Several V genes participate in the early phenyloxazolone response in various combinations

Seventeen monoclonal anti-2-phenyloxazolone antibodies from the early (day 7) primary response were partially sequenced with an mRNA method. Ten antibodies expressed the VH-Ox1 gene. The remaining seven express at least four but probably six different germ-line VH genes belonging to Dildrop's groups 1, 5, 6 and 7 (Immunol. Today 1984. 5: 85). Two of them have been met before in other antibodies, one (group 6) in J606 and the other (group 7) in antibodies to the influenza virus hemagglutinin. Eleven kappa chains were partially sequenced and five of them (all VH-Ox1 antibodies) express the V kappa-Ox1 gene. One expresses another germ-line gene of the V kappa-Ox1 family, one the V kappa 89.4 gene, three the V kappa 45.1 gene and one a new V kappa gene. The V kappa 45.1 gene was found to form anti-phOx antibodies with two new VH genes. The frequency of somatic mutations in day 7 antibodies was estimated by comparing germ-line sequences and antibody sequences. It is low (one mutation per 2500 nucleotides sequenced), twenty times lower than in antibodies obtained a week later. Two anti-idiotype antisera (495 and 260) are useful in the typing of monoclonal antibodies. 260 bound only to antibodies coded by both VH-Ox1 and V kappa-Ox1 genes. 495 bound strongly to antibodies coded by the VH-Ox1 gene and weakly to antibodies coded by the (related) VH101 gene regardless of the light chain partner.     

Combinatorial association of V genes: one VH gene codes for three non-cross-reactive monoclonal antibodies each specific for a different antigen (phoxazolone, NP or gat)

Two anti-phenyloxazolone (phOx3) and one anti-GAT MAbs from C57BL mice are shown to be coded by VH gene 186.2. This gene has been found earlier to code for several anti-NP (NNP) antibodies (Bothwell et al., 1981) and anti-GT antibodies (Rocca-Serra et al., 1983; Carmack and Pincus, 1986). The L chain partner of the VH 186.2 gene is different in anti-NP and anti-GAT antibodies (Bothwell et al., 1981; Rocca-Serra et al., 1983; Carmack and Pincus, 1986); in anti-phOx antibodies two new unrelated kappa chain V regions were found. Both of the new VK genes involved code frequently for anti-phOx antibodies in BALB/c mice but then with different VH genes. We tested five 186.2-coded antibodies for cross-reactions. Four antibodies were specific, one bound only to NNP, one only to phOx and two only to GT (GAT). The fifth antibody (anti-phOx) bound also to NNP, GAT and ABA-HOP though probably with a low affinity. This is the first demonstration that one V gene can code for three different antibody specificities. It emphasizes the role of the combinatorial element in antibody diversity.     

V genes of oxazolone antibodies in 10 strains of mice

One pair of V genes (V kappa 45.1 and V11) code for a great portion of phenyloxazolone (anti-phOx) antibodies in 10 strains of mice. This combination replaces the first-known major combination VHOx1-V kappa Ox1 in some strains, and is important in most strains. C57BL/10 and SJL mice have an additional subset of antibodies encoded by genes V kappa 45.1 and V13 (a relative of V11). All three genes involved (V kappa 45.1, V11 and V13) have "allelic" variation. Four alleles of V11 were found, one in Igh haplotypes a, c and g, the second in haplotypes d, j and n, the third in b, and the fourth in f. The most distant alleles d, j, n and f had 10 nucleotide differences out of 429 determined (97.7% homology). Only one allele of the V13 gene was found from anti-phOx hybridomas but two others have been published. Three alleles of the V kappa 45.1 gene were found; one in NZB mice (Ig kappa haplotype b) another in CE (haplotype f), and the third in eight strains including representatives of three Ig kappa haplotypes (a, c and e). The three alleles had greater than 99.0% homology. The V11 and V13 genes that code for anti-phOx antibodies in C57BL/10 and SJL mice were different from the related genes found from the C57BL/10 germ line. C57BL/10 mice must have a chromosome bearing two V11 and two V13 genes. RF mice were found to have two V11 genes, and both code for anti-phOx antibodies. Our data show that the majority of antibodies in the anti-phOx response are encoded by the same restricted collection of V genes in most mouse strains. Antibody responses appear to be no less heritable than other functions of the body.     

The same few V genes account for a majority of oxazolone antibodies in most mouse strains.

The early primary anti-phenyloxazolone antibodies of 12 mouse strains were studied by determining proportions of two defined subsets id495 (the classical phOx idiotype) and id350. Id495-positive antibodies bear an H chain encoded by VHOx1 gene (family Q52) and an L chain usually coded for by VKOx1 but occasionally by other VK genes. Id350-positive antibodies are encoded by a VK gene VK45.1, and usually by a VH gene of the S107 family. All 12 strains (representing nine H-chain and four kappa-chain haplotypes) produced id350-positive anti-phOx antibodies. While id495 is the predominant major subset in the BALB/c response (originally studied), id350 seems to be the predominant subset of early anti-phOx antibodies in the mouse species. The combined proportion of the two subsets varied from ca. 50 to almost 100% of the total in all strains except C57BL.     

Quantitative representation of two germ-line V genes in the early antibody response to 2-phenyloxazolone

Early anti-phenyloxazolone antibodies of BALB/c mice include a subset that bears the nearly or totally unmutated VH-Ox1 sequence. A fraction of this subset also bears the nearly or totally unmutated V kappa-Ox1 sequence. The whole subset is recognized by an anti-idiotype serum 495 and the VH-Ox1/V kappa-Ox1 fraction also by another anti-idiotype serum 260. Frequencies of the VH-Ox1 subset and its V kappa-Ox1 fraction in early IgM and IgG antibodies were determined by typing hybridomas with anti-idiotype antisera. The whole subset appears to make up approximately one half of IgG antibodies, two thirds of this being 495+/260+ in both isotypes. IgM data are less certain but the same frequencies may be valid. Affinities of 495+/260+ antibodies ranged from 1.3 X 10(6) to 11 X 10(6), affinities of 495+/260- antibodies from 0.47 X 10(6) to 1.1 X 10(6), and affinities of doubly negative antibodies were less than 0.41 X 10(6). High affinity is probably an explanation for the high proportion (one third) of the 495+/260+ antibodies in the early response. Doubly negative (and low-affinity) hybridomas may not have been classified as producers of phenyloxazolone antibodies in earlier studies, and this could explain the still higher reported frequency (73%) of VH-Ox1/V kappa-Ox1 antibodies.     

An immunoglobulin V gene polymorphism in the rat

Anti-phenyloxazolone (phOx) antibodies of different AVN rats (primary response) share several isoelectric focusing bands. These bands were not shared by antibodies of some other rat strains, including DA. An anti-idiotype reagent was prepared (in rabbits) that bound radioactive anti-phOx antibodies of AVN rats but not normal AVN immunoglobulin. This binding was strongly inhibited by AVN anti-phOx anti-sera, but not by AVN anti-BOC-p-azobenzene arsonate-tyrosine antisera or DA anti-phOx antisera. Anti-phOx antisera of (AVN x D A)F₁ rats were also strongly inhibitory indicating the presence of the idiotype (Ox-r1). Antisera of backcross rats (AVN x DA) x DA either resembled F₁ hybrid sera (31 rats) or DA sera (23 rats). The data suggest that the presence of idiotype Ox-r1 is controlled by one gene, or genes linked to each other. The gene(s) is not linked to the Ig kappa chain locus. It may be a V gene of the Ig H chain.     

A Gene of the Immunoglobulin H-Chain Cluster Controls the Murine Antibody Response to Pneumococcal Polysaccharide Type 14

Mice of various strains were immunized with pneumococcal polysaccharide type 14 (pneumo-14), and their anti-pneumo-14 antibodies were measured by the Farr test. Mice of strains BALB/c, ST/b, NZB and CBA (Ig allotypes a, e or j) had 300-1700 ng of antibody nitrogen per millilitre of serum on day 7. The corresponding values for C57BL/Ka, RF or AKR mice (allotypes b, c or d) were 40-300 ng/ml. Two families of congenic strains were tested, one with the C57BL and the other with the BALB/c background genome. Their response was either high or low depending on the VH genes, and other gene loci had little effect on the concentration of anti-pneumo-14 antibodies.     

Immunologic memory to phosphorylcholine. VI. Heterogeneity in light chain gene expression

BALB/c mice immunized with phosphorylcholine-conjugated keyhole limpet hemocyanin (PC-KLH) produce two types of anti-PC antibodies, designated group I and group II, which differ in their fine specificity and idiotype expression. Group II hybridomas can utilize VH genes and VL genes (in particular, V kappa 1-3) distinct from those expressed in the group I-like anti-PC myelomas. Here we have analyzed additional anti-PC hybridomas from BALB/c and (CBA/N X BALB/c)F1 male mice and also anti-PC antibodies purified from BALB/c and C57BL/6N antisera. Isoelectric focusing indicates that one of the group II hybridomas utilizes V kappa 1-3 and that related L chains are expressed in a major portion of group II serum antibodies. Other group II antibodies in antisera express different L chains, some of which are presently unidentified. However, isoelectric focusing analysis also indicates that the L chains of some group II hybridomas and serum antibodies are related to those found in the group I anti-PC myelomas and group I hybridoma and serum antibodies. In addition, one hybridoma was found to utilize lambda 2. Thus, it appears that the anti-PC antibodies with group II-like fine specificity can utilize a variety of VL genes related to, or distinct from, those expressed in group I antibodies.     

Specificity and variable region cDNA sequence of an isogeneic monoclonal antiidiotype to an anti-alpha(1----6)dextran.

We have characterized a monoclonal isogeneic antiidiotype, IdB5.7, from a BALB/c mouse immunized with the anti-alpha(1----6)dextran C57BL/6 45.21.1. It defined a hapten-inhibitable idiotope expressed on four of the 2 myeloma and 37 hybridoma anti-alpha(1----6)dextrans tested. Sequence comparison of Id+ and Id- anti-alpha(1----6)dextrans suggested that two extra amino acids at VH 100A and 100B and different residues at VH 101 abolish the expression of the idiotope in the Id- anti-alpha(1----6)dextrans. Sequence analysis of the VH of IdB5.7 showed a CDR1 longer than usual and a D segment in CDR3 formed by the fusion of two D minigenes. The IdB5.7 V kappa uses the V kappa 1 germline gene K5.1 with a few substitutions. The D-D fusion in VH CDR3 is a feature which has been reported in several other antiidiotypic antibodies.     

Lack of somatic mutation in a kappa light chain transgene

Analysis of mice transgenic for immunoglobulin genes should allow definition of the cis-acting DNA sequences required to target somatic mutation to antibody V genes. We have looked for mutations in a chimeric kappa transgene encoding a V region specific for the hapten 2-phenyloxazolone (phOx) linked to a rat C kappa gene. Two independent lines of transgenic mice were hyperimmunized with phOx and splenic hybridomas established. In B cells that had been selected by antigen and which used mouse anti-phOx genes, the endogenous sequences were found to be mutated whereas the transgene remained unchanged. These results suggest either that (a) if the transgene is a "passenger" gene expressed at a low level, transgene mutation is a rare event, or that (b) sequences far from the kappa coding region are necessary to direct somatic mutation.     

Two major idiotypes in mouse anti-(4-hydroxy-3-nitro-phenyl)acetyl (NP) antibodies are controlled by "allelic" genes

Anti-NP [(4-hydroxy-3-nitro-phenyl)acetyl)] antibodies from the primary response of BALB/c mice contain a major idiotype NP-a that is controlled by an allotype-linked gene VHNPa. A new strain distribution pattern for a VH marker was discovered: strains BALB/c, RF, DBA, RIII and SM were positive, and strains C57BL/6, SJL, CBA, A/J, CE, AKR and NZB were negative for the idiotype NP-a. NP-a idiotype chared many characteristics with previously described idiotype NP-b and, therefore, allelism was suggested between them. Both idiotypes have lambda light chains, both seem to be conservative in evolution, both are predominant early in the antibody response. Later during the response, antibodies become increasingly idiotype-negative while at the same time, homogeneous isoelectric focusing patterns become very heterogeneous. The study of VH recombinant strains supported the concept of allelism because in every case studied, the idiotype were mutually exclusive. (C57BL/6 X BALB/c)F1 mice expressed idiotypes NP-a and NP-b regularly and in approximately equal amounts.     

Genetic control of the immune response to the L-Glu60-L-Ala30-L-Tyr10 (GAT) terpolymer. V. Three types of idiotypic specificities on BALB/c anti-GAT antibodies

Three types of idiotypic specificities compose the major idiotype of anti-poly (L-Glu60-L-Ala30-L-Tyr10) (GAT) antibodies from BALB/c mice (idiotype termed GAT-715). Assays have been designed to analyzed and study the distribution of these specificities. The highly conserved idiotypic specificity (h.c.GAT) has been assayed by the binding of serum 715-7A4 to radiolabeled rat anti-GAT antibodies. Guinea pig and mouse anti-GAT antisera all express the same h.c.GAT specificity. The public specificity (p.GAT) has been shown to be present in an identical form in all anti-GAT antisera from all strains of mice studied. The assay used for p.GAT was the binding of serum 715-7A4 to C57BL/6 anti-GAT antibodies that express only p.GAT. Finally, the strain-restricted specificity s.r.GAT has also been investigated by radioimmunoassay; this specificity is expressed only by strains BALB/c, BALB/b, BUB/J, DBA/2, DBA/1 and ATL. This expression is independent of known allotypic markers. However, the expression of the s.r.GAT specificity of BALB/c mice follows the genetic distribution of VH genes of BALB/c origin indicating that s.r.GAT can be considered as a genetic marker of some VH gene(s) involved in the specific immune response to the GAT terpolymer.     

Diversity and somatic hypermutation of the Ig VHDJH,V kappa J kappa,and V lambda J lambda gene segments in lymphoma B cells: relevance to the origin of the neoplastic B cell clone

Burkitt's lymphoma (BL) is a malignancy of B cells characterized by chromosomal translocations involving the immunoglobulin (Ig) and c-MYC gene loci. To address the putative role of antigen in the clonal expansion of these neoplastic B cells, we analyzed the VHDJH and VLJL gene segments expressed by the established cell lines derived from six endemic BL and six sporadic BL. Eight BL cell lines used genes of the VH3 family, two of the VH4, and two of the VH1. Eight VL chains were kappa (four members of the V kappa3, two of the V kappa1, and two of the V kappa2 subgroups) and four lambda (three members of the V lambda1 and one of the Vl ambda3 subgroup). The VH gene utilization was stochastic (i.e., it reflected the relative representation of the different VH gene family members in the human haploid genome). In contrast, the VL gene utilization was skewed toward the overutilization of the V kappa3 and V lambda1 gene subgroups. When compared with those of the respective germline genes, the sequences of the expressed Ig VDJ genes displayed nucleotide differences that resulted from somatic hypermutation. In three endemic and three sporadic BL cells, nucleotide changes yielding amino acid substitutions segregated within the complementarity determining region, indicating the application of a positive pressure for replacement mutations and suggesting that these neoplastic lymphocytes underwent a process of clonal selection driven by antigen, perhaps emerging from or transitioning through germinal centers.     

Correlation between immune maturation and idiotypic network recognition

The maturation of T-dependent humoral immune responses is mediated by somatic mutations. Antigen selection is one mechanism for the activation of B cell clones which express antibodies with progressively increased affinity and which are derived as somatic variants from germ-line-encoded genes. However, the emergence of B cell clones secreting rather low-affinity antibodies and the shift to alternative germ-line V region gene combinations during secondary and tertiary responses cannot be explained by antigen selection. It has been considered that idiotypic suppression may favor this clonal shift. Such an involvement would require that idiotypic recognition in the syngeneic host must be highly restricted to private idiotopes of each clone sequentially activated during immune maturation. To test this possibility, we produced 19 syngeneic anti-idiotypic antibodies to the germ-line-encoded major Ox1 idiotype (IgM-Id_Ox1 H11.5) of the anti-2-phenyl-oxazolone (phOx) immune response in BALB/c mice. The fine specificity of these anti-Id_Ox1 was tested with a set of anti-phOx monoclonal antibodies, representing the first steps of maturation. About half of the anti-Id_Ox1 showed almost no reactivity with the Id_Ox1 after the switch to IgG and none of the anti-Id_Ox1 reacted with anti-phOx antibodies which carried a glycine or histidine instead of arginine as the middle amino acid of the D region. These observations suggest a strong correlation between immune maturation and the idiotypic network. A model is presented in which idiotypic suppression may function as a driving force for diversification and maturation of the antigen-induced immune response.     

Comparison between hybridoma and Fab/phage anti-RhD: their V gene usage and pairings

Our 11 anti-RhD's in conjunction with 37 previously published RhD antibodies, produced by hybridoma technology were analysed for germline gene usage and restriction in VH and VL pairings. The 17 VH germline genes used by the hybridoma anti-RhD IgG were derived from 4 VH families (VH1, VH2, VH3 and VH4). Eighteen kappa chains were restricted to only 5 germline genes from only 2 V kappa families (V kappa 1 and V kappa 3). However, the 13 lambda chains were not as restricted, using 10 V lambda germline genes from 4 families (V lambda 1, V lambda 2, V lambda 3 and V lambda 8). Fifty six unique Fab/phage anti-RhD were also analysed. In all cases the Fab/phage VH germline genes were derived from the VH3 family (41/41). The 29 kappa chains were restricted to 4 germline genes primarily from V kappa 1 (97%) and the 24 lambda chains used 10 V lambda germline genes from 5 families (V lambda 1, V lambda 2, V lambda 3, V lambda 4 and V lambda 7). The VH germline genes of the Fab/phage were restricted to 4 of the 17 used by the hybridoma anti-RhD IgG (DP46, DP49, DP50 and DP77). Ninety percent of the Fab/phage were restricted to 1 of the 5 V kappa germline genes used by the IgG (DPK9). However, the repertoire of the V lambda germline genes used in these two systems is different, with analysis showing greater diversity in V lambda gene usage with 8 unique germline genes used by 76% Fab/phage compared to 4 unique genes used by 46% of the IgG hybridoma anti-RhD.     

Restricted usage of VH and V kappa genes by murine monoclonal antibodies against 3-fucosyllactosamine

We are studying the structure and regulation of murine antibodies against the 3-fucosyllactosamine antigenic determinant. Analysis of the sequences of seven BALB/c IgM, kappa monoclonal antibodies (mAb), obtained from four fusions, indicates that these antibodies exhibit restriction in their usage of VH and VL genes. Based on a combination of mRNA sequences and Southern filter hybridization data, all seven light chains are encoded by V kappa 24B and J kappa 1 gene segments. Complete mRNA sequences of the heavy chains revealed that all seven mAb are encoded by VH441, six antibodies are encoded by JH4 and one uses a JH3 gene segment. The VH441 gene segment and all seven mAb contain a potential glycosylation site at Asn 58 in complementarity-determining region (CDR)2. In contrast to the similarity of the VH regions, the heavy chain CDR3 segments exhibit considerable heterogeneity. They are encoded by three D segments, they vary in length from 7-9 amino acids and display differences in their deduced amino acid sequences. The VH441 gene segment also encodes antibodies against four other carbohydrate antigens, levan, galactan, dextran and galactosyl globoside. The use of a single gene segment to encode antibodies against five different antigens suggests that the domain encoded by VH441 might be particularly well adapted for forming sites that bind carbohydrate determinants. Glycosylation of CDR2 might contribute to the unique properties of this VH domain.     

Anti-Inulin [β-(2→1)-Linked Polyfructose] and Anti-Grass Levan [β-(2→6)-Linked Polyfructose] Antibody Response in Mice

Anti-inulin [β-(2 → 1) polyfructosan Brucella abortus (InuBA)] and anti-grass levan [β-(2 → 6) polyfructosan] antibody responses in BALB/c and C57BL mice and in their F₁ and backcross progeny, as well as in immunoglobulin congenic and Bailey recombinant inbred strains derived from BALB/c and C57BL mice, were examined. The anti-inulin antibodies could accommodate both β-(2 → 1)- and β-(2 → 6)-linked polyfructosans, and 97% of the anti-inulin plaque-forming cells (PFC) from BALB/c mice expressed the cross-reactive idiotypes (InuIdX) shared by the BALB/c inulin- and levan-binding myeloma proteins. Of the C57BL mice, only 25% produced high anti-inulin response, and none exhibited the InuIdX of BALB/c anti-inulin antibodies. The percentages of InuIdX⁺ anti-inulin PFC were also examined in other strains with high anti-inulin response. In C58 and AL mice, 80% of anti-inulin PFC were InuIdX⁺, whereas in A/He and RIII mice, only 40% were InuIdX⁺. All strains examined developed high anti-grass levan response, and the antibodies were specific for β-(2 → 6) structures and did not exhibit InuIdX. Comparison of the magnitude of the anti-inulin antibody titers in response to InuBA in BALB/c, C57BL, and their F₁ and backcross progeny, as well as in immunoglobulin congenic (i.e., B.C-8, BAB-14, and C.B-20) and recombinant inbred strains derived from BALB/c and C57BL mice, showed that all mice having the IgCH^a(BALB/c) allotype gave high anti-inulin response. In addition to the InuIdX structural genes, the effects of allotype-linked or unlinked “regulatory” genes were also indicated by the lower anti-inulin response in B.C-8 and BAB-14 mice compared with BALB/c mice and the higher anti-inulin response in C.B-20 mice compared with C57BL mice. A multigene interaction in controlling the production of the anti-inulin antibodies was implicated.     

Characterization, specificity, and IgV gene usage of anti-lymphocyte monoclonal antibodies from perinatal mice.

Previous studies have shown that CD5+ B cells predominate during development of the immune system and frequently secrete self-reactive antibodies, some of which appear to influence the development of the adult B cell repertoire. In addition, we now show that a high frequency of perinatally derived antibodies react with lymphocytes. Hybridomas derived from perinatal liver and splenic B cells and from spleens of adult BALB/c and C57BL/6 mice were screened by immunofluorescence on thymocytes. Anti-lymphocyte antibodies, all of the IgM isotype, were detected at a high frequency from perinatal fusions, but none were obtained from adult mice. These anti-lymphocyte mAbs were heterogeneous because they stained different subsets of peripheral T and B lymphocytes. Although the antigens recognized by these mAbs were heterogeneous with respect to their sensitivity to a variety of enzymes, 13 of the 19 mAbs recognized epitopes which were modulated by phosphatidylinositol-phospholipase C treatment. Inhibition experiments suggested that six of these 13 mAbs shared the same molecular specificity, and that they recognized the same T cell subset (62% of CD4+ and 98% of CD8+ cells). Furthermore, three of these mAbs immunoprecipitated the same 100 kDa protein from thymocytes (70 kDa in reducing conditions). The related molecular specificity of some anti-lymphocyte mAbs was also reflected by their restricted V gene usage. Three of the five mAbs specific for the 100 kDa protein used very similar or identical germline SM7 VH genes. In addition to using the same germline D and JH genes, they also exhibited identical VH-D-JH joins, despite originating from distinct fusions. Analysis of light chains also showed some restriction by preferential use of germline V kappa 4 and J kappa 5 genes. Together, these results suggest that the restricted antibody repertoire characteristic of mouse fetal and neonatal B cells is also reflected in the production of anti-lymphocyte antibodies. These B cells appear consistently in early development, use germline V genes, and express a characteristic VH-D-JH join.     

Selective strain distribution pattern of a germline VH gene for a pathogenic anti-DNA autoantibody family

Autoimmune NZB mice rarely develop nephritis, but the SNF1, progeny of Crosses between NZB and the normal SWR strain uniformly develop severe lupus nephritis, indicating that the normal SWR strain makes a genetic contribution to the development of nephritis. The SNF1 mice produce a select population of cationic IgG anti-DNA autoantibodies that share a recurrent cross-reactive idiotype called Id564 and these autoantibodies play a prominent role in the development of nephritis. These pathogenic autoantibodies of SNF1 possess the IgCH allotype of the SWR, indicating their origin from the normal parent. The leader-VH sequences of these Id564+ pathogenic anti-DNA autoantibodies are highly homologous and they are also related by 95% homology to a germline gene of normal C57BL/6 mice, called VH-23, that is a member of an anti-NP antibody gene family. Herein, we cloned the flanking and coding regions of the expressed VHDJH genes of the anti-DNA mAb 564, the prototype member of the pathogenic Id564 family. By restriction analysis and partial sequencing, we found that the VH564 gene is related but distinct in its 5' flanking region from all of the known anti-NP VH genes of C57BL/6 and BALB/c mice. Hybridization with four probes complementary to different segments of the flanking and coding regions of the expressed VH564 gene indicated that the germline gene for VH564 is contained in an approximately 5.2 kb EcoRI fragment of SWR genomic DNA. Moreover, high stringency hybridization with oligonucleotide probes complementary to unique CDR2 and 5' flanking sequences of the expressed VH564 gene revealed that the 'approximately 5.2 kb' germline allele for VH564 that is possessed by the normal SWR parental strain is lacking in the NZB parental strain. C57BL/6 mice also lack this allele of the anti-DNA VH564 germline gene, although this strain possesses the highly homologous, anti-NP-related VH-23 germline gene. Thus germline VH genes for certain pathogenic autoantibodies may have a selective strain distribution pattern.     

Resistance and susceptibility of mice to bacterial infection: genetics of listeriosis.

A survey of various strains of mice showed distinct differences in resistance or susceptibility to Listeria monocytogenes. C57B1, related sublines, NZB, and SJL were resistant to Listeria, whereas BALB/c, CBA, A, DBA/1, C3H, LP.RIII, 129, and WB were susceptible. The gene(s) responsible for resistance and susceptibility to Listeria were studied in detail. C57BL6/6, B10.D2, and B10.A mice were 100 times more resistant than were BALB/c, CBA, and A. Resistance of the (C57B1/6 X BALB/C)F1 was intermediate between the two parents, suggesting partial penetration of a dominant gene. Backcross studies in which the (C57B1/6 X BALB/c)F1 were crossed with the susceptible BALB/c parent suggested that a single gene or group of linked genes were the major determinant of resistance, although the possibility that other genes exerted a modifying influence was not excluded. By using the backcross and various congenic and recombinant mice, linkage of the genes involved to the H-1, H-2, H-3, H-4, H-7, or H-8 loci, to the immunoglobulin allotype, to the Thy-1 gene, to the Hc gene specifying C5, or to coat color genes (B, c) was excluded. There was no difference in the response of males and females. In all studies, the powerful overriding influence of the C57B1 genome was evident.