Alkaline phosphatase-positive B cell lymphomas

Alkaline phosphatase (ALP) activity of 70 cases of non-Hodgkin's lymphomas of the B-cell type was studied. ALP activity was found in malignant lymphoma (ML), follicular, small cleaved cell (1/5 cases); ML, diffuse, small cleaved cell (3/13 cases); and mantle zone lymphoma (intermediate lymphocytic lymphoma) (2/2 cases). The ALP-positive neoplastic cells simultaneously displayed the characteristic immunophenotype of mantle zone (MZ) B lymphocytes of secondary follicle (SIg D+, BA-1+, IL-2R+ and Leu-1+). All other B-cell lymphomas, including ML, follicular, mixed small cleaved and large cell (9 cases); ML, follicular, large cell (4 cases); ML, mixed small and large cell (7 cases); ML, diffuse, large cell (27 cases); and ML, small noncleaved cell (3 cases), were consistently negative for ALP. The present study indicates that ALP-positive lymphomas including follicular lymphomas and diffuse lymphomas may be neoplastic counterparts of ALP-positive MZ B lymphocytes.     

Lymphocyte subpopulations in peripheral blood in primary sclerosing cholangitis

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a chronic disease of autoimmunological etiology, leading to inflammation, destruction and atrophy of the bile ducts. The aim of the study was to determine peripheral lymphocyte B, T, and NK cells in PSC. METHODOLOGY: The estimation of peripheral blood lymphocytes in 17 patients (54+/-12 years old) with PSC was carried out; the control group consisted of 27 subjects (38+/-11 years). The following T lymphocyte subpopulations were determined using duo color flow cytometry: CD3+, CD4+, CD8+, CD3++HLA DR+, B cells CD19+, and NK cells CD16+ +CD56+. RESULTS: In PSC we observed doubled increase in activated T lymphocytes of CD3+ +HLA DR+ phenotype as compared to healthy subjects (7.9% vs. 2.7%, p<0.01) and NK cells (12.6% vs. 10.3%, respectively, p<0.05). There were no significant differences in the composition of CD3+, CD4+, and CD8+. In peripheral blood we noted, in patients with PSC, a decrease in B lymphocytes (11.2% vs. 12.3%, p<0.19). CONCLUSIONS: The examinations showed that activated T (HLA DR+) lymphocytes and NK cells played an important role in development of PSC.     

The presence of active C1 (C-1) on peripheral human lymphocytes.

We have shown that the first component of complement C1 is present in an active form on the surface of washed human peripheral lymphocytes but not on platelets or erythrocytes. This active C1 (C-1) was detected by its ability to transfer to sensitized cells carrying C4, i.e., EAC4, forming EAC-1,4. Active C1 was also able to consume C4. Treatment of these lymphocytes with 0.02 M EDTA removed C-1. EDTA-treated lymphocytes were able to bind exogenous purified human C-1. Comparative studies with sentized erythrocytes (EA) and EDTA treated lymphocytes showed that although fewer molecules of exogenous C1 could bind to the EDTA-treated lymphocytes than to EA, the consumption of C4 by C-1 bound to lymphocytes was significantly higher than that observed with EAC-1. When lymphocytes obtained from 2 patients with chronic lymphocytic leukemia and hypocomplementemia were tested, the release of C1, the C4 consumption and the binding of C-1 to EDTA-treated cells were highly inefficient.     

Phenotype study of fresh and cultured hairy cells with the use of immunologic markers and electron microscopy

The phenotype of fresh and cultured leukemic cells from patients with hairy cell leukemia was studied using a panel of monoclonal antibodies in addition to the detection of peroxidase activity under electron microscopy. In fresh samples, the leukemic cells from 11 patients displayed predominantly a B phenotype, as judged by their reactivity with the B1 monoclonal antibody and surface immunoglobulin expression. Ultrastructural peroxidase activity, characteristic of hairy cells, was observed in all cases studied. When hairy cells were cultured in the presence of phytohemagglutinin and irradiated T cells, their phenotype converted from surface Ig+, B1+, OKT3-, OKT11- to surface Ig-, B1+, OKT3-, OKT11+. In contrast, the peroxidase activity remained unchanged. Some hairy cells were also OKM1+, but no conclusion could be made about the MO2 antigen, a more specific marker of monocytes. The variability of the phenotype in vivo and in vitro indicates that reliable markers are required for identifying hairy cells. When studied together, the staining by B1 monoclonal antibody and the ultrastructural detection of peroxidase, enable the identification of hairy cells with certainty.     

Clinical relevance of immunologic phenotype in diffuse large cell lymphoma

The immunologic phenotypes of 78 diffuse large cell lymphomas were determined by an immunoperoxidase technique using a panel of monoclonal antibodies. The phenotypes were correlated with clinical and morphological parameters by univariate and multivariate analysis. Forty-one lymphomas (53%) expressed immunoglobulin (Ig+). Of the 37 cases that did not express immunoglobulin (Ig-), 9 expressed T cell antigens. Although the T cell phenotypes were antigenically heterogeneous, all cases represented mature T cell phenotypes. The majority of the remaining 28 cases expressed the B cell-associated antigen, B1. At 5 yr, actuarial survival for the Ig- patients was 63%, compared with 15% for the Ig+ patients. A significantly greater proportion of patients with Ig+ lymphomas were over the age of 65 at diagnosis. All of the 9 patients with marrow involvement were Ig+. Multiple factors were analyzed by the Cox regression procedure for their impact on survival, including antigenic profile, histologic grade, morphological classification, and numerous clinical parameters previously recognized to be of prognostic significance. In this analysis, stage, age greater than 65 yr, systemic symptoms, and marrow involvement had the greatest influence on survival. The survival difference between Ig- and Ig+ patients is explained by a higher proportion of Ig+ patients with these unfavorable prognostic factors. With our current immunologic methods, retrospective cell phenotyping analysis has not provided independent prognostic significance in diffuse large cell lymphoma. A prospective evaluation of similarly treated patients is needed to characterize the influence of phenotype fully and to determine its potential usefulness for therapy.     

Peripheral blood T,B, and NK cells in relation to histological hepatitis activity and fibrosis stage in chronic hepatitis C

BACKGROUND/AIMS: Many data on the pathogenesis of chronic hepatitis C have pointed to host's immune system disorders and a high variety of virus. However, there are no known criteria that could prognose the course of chronic hepatitis C infection. The analysis of T and B lymphocyte subpopulations in the peripheral blood was undertaken in patients with chronic hepatitis C of more than 6 months of duration. METHODOLOGY: Fluorescein isothiocyanate or phycoerythryne conjugated monoclonal antibodies for CD3+, CD4+, CD8+, CD19+, CD3++ HLA DR+, CD16++ CD56+ were used. The correlation between histological hepatitis activity and fibrosis (according Scheuer's scale) and the distribution of lymphocytes in the peripheral blood was sought. RESULTS: All patients with chronic hepatitis showed statistically significant increase in active lymphocytes CD3++ HLA DR+ and CD16++ CD56+ NK cells in peripheral blood. We observed the correlation between these cells and histological hepatitis activity and fibrosis. There was no correlation between the value of CD3+ and CD8+ cells and the stage of liver failure. In the early stage of chronic hepatitis C we noted decrease CD4+ cells with increase B cells CD19+. CD4+/CD8+ ratio was maintained as slightly decreased in chronic hepatitis C in favor of lymphocytes CD8+. CONCLUSIONS: The results show the correlation between peripheral blood value of activated T cell (HLA DR+) and NK cells with histological activity and fibrosis in chronic hepatitis C. Lymphocyte T (CD4+, CD8+) and B (CD19+) did not correlate with grade and stage of hepatitis C.     

A simplified one-step procedure for the simultaneous determination of complement receptor lymphocytes and lymphocytes with membrane-bound immunoglobulins.

A simple one-step procedure for the demonstration of complement receptor lymphocytes (CRL) with complement-coated bacteria (BC) as indicator particles is described. With this assay the percentage of CRL in normal peripheral blood ranged between 6 and 21% (mean 11%). In a separately performed combined assay for lymphocytes with membrane-bound immunoglobulins (M-Ig) and lymphocytes, which form rosettes with complement-coated bacteria (BC-RFC), four different fractions of lymphocytes could be detected: (M-Ig+-BC+, M-Ig+-BC-,M-Ig--BC+, M-Ig--BC-). These results suggest that the subpopulation of lymphocytes with complement receptor sites overlaps with, but is not totally identical with the lymphocyte subpopulation bearing Ig on the surface.     

Evolution of Ig- and T-cell receptor gene configuration in a Ph1+ hybrid leukemia patient.

In a longitudinal study of a 32-year-old male with Ph1+ hybrid leukemia we have followed the immunophenotype and configuration of Ig- and TCR genes during the course of different chemotherapy regimens directed first against the myeloid and later against the lymphoid components of the disease. We identified changes in all parameters, interpretable as an evolution of the malignant clone resulting in a leukemic switch towards a more lymphoid character. Thus, while the expression of the myeloid antigens CD13 and CD33 decreased, that of CD10 (CALLA) and CD20 (B1) increased. Moreover, while the configuration of the Ig heavy and light chain lambda genes remained constant during the whole period of treatment, that of the Ig light chain kappa gene and TCR beta gene displayed extensive rearrangements after initiation of ALL therapy. Since this patient represents a de novo acute leukemia as evaluated by location of the translocation-breakpoint on chromosome 22, our data clearly indicate that Ig- and TCR gene rearrangements might prove a valuable addition in monitoring Ph1+ hybrid leukemias, providing guidelines for optimizing chemotherapy.     

Heterogeneity of T-lymphocyte chronic lymphatic leukaemia (CLL). Study with conventional surface markers and monoclonal antibodies

Lymphocyte surface markers (E-SRBC, EAC, EA gamma and SmIg) and monoclonal antibodies (OKT3, OKT4, OKT8 and OKIa) were used to characterise the blood and bone marrow lymphocytes of T-cell CLL (8 patients). The diagnosis of T-cell CLL was made primarily as the majority of blood lymphocytes formed E-SRBC in each patient. Other markers-EAC, EA gamma and SmIg--showed different patterns of association with E-SRBC. These findings considered together described 4 different phenotypes amongst these patients: (a) E+ (3 patients), (b) E+, EAC+ (1 patient), (c) E+, EA gamma + (2 patients), and (d) E+, SmIg+ (2 patients). Similarly, 4 different groups were defined with the help of monoclonal antibodies. Helper T-cell (3 patients) and suppressor T-cell (1 patient) CLL showed predominantly helper T- and suppressor T-lymphocytes respectively. Mixed T-cell CLL (1 patient) comprised an equal proportion of both subpopulations, while the remaining 3 patients, with excess of one or other subpopulations along with a considerable proportion of Ia antigen-bearing lymphocytes, formed the indeterminate cell type CLL.     

A novel leukemia cell line, MR-87, with positive Philadelphia chromosome and negative breakpoint cluster region rearrangement coexpressing myeloid and early B-cell markers

We developed a Philadelphia chromosome (Ph) positive cell line, designated MR-87, from a 4-year-old boy with Ph+-acute leukemia. MR-87 cells grew in single cell suspensions with a doubling time of 120 to 144 hours. Both MR-87 and original leukemia cells were positive for myeloperoxidase (MPO) and myeloid antigen CD13. These cells exhibited the early B-cell phenotype, ie, terminal deoxynucleotidyl transferase+, Ia+, CD19+, and CD10+. Rearrangement of the immunoglobulin heavy chain was confirmed in both. Approximately 80% of MR-87 cells coexpressed CD13 and lymphoid antigens CD10 or CD19, as confirmed by a two-color analysis. Simultaneous expression of MPO and CD19 on a single MR-87 cell was demonstrated at ultrastructural level. Thus, MR-87 is a Ph+ leukemia cell line exhibiting a hybrid phenotype. The breakpoint cluster region (bcr) was not rearranged in the MR-87 cells and subsequent analysis using antisera revealed that these cells expressed a novel protein, P190c-abl, which was immunoprecipitated with anti-abl and anti-phosphotyrosine antibodies. The MR-87 line will be most useful for investigating the biology and pathogenesis of Ph+ bcr- acute leukemia.     

Ontogeny of murine B lymphocytes: sequence of B-cell differentiation from surface-immunoglobulin-negative precursors to plasma cells.

Among bone-marrow-derived (B) lymphocytes exist subpopulations of cells that can be induced to express the markers: surface immunoglobulin (Ig), the antigen associated with the immune response gene (Ia), and the receptor for the third complement component (CR). Inducible cells for the first two markers are found in bone marrow, and inducible cells for all three are in spleen. Experiments were designed to determine whether induction involves a single precursor cell population that on triggering with lipopolysaccharide expresses all three surface markers, or three separate precursor cell populations each of which expresses a single marker. Specific B cell subpopulations were eliminated by treatment with anti-Ig or anti-Ia and complement, or by rosette formation with erythrocytes-antibody-complement followed by differential centrifugation, and surviving cells were subsequently tested for inducibility of the three B cell markers. After anti-Ig cytolysis only Ig, but not Ia and CR, could be induced, implying that the Ia- and the CR-inducible cells are Ig+. Similarly, after anti-Ia cytolysis Ig and Ia but not CR could be induced. Thus, CR-inducible cells must have the Ig+Ia+ phenotype. Elimination of CR+ cells did not affect the induction of Ig, Ia, or CR from their precursors. None of the three elimination experiments affected the conversion of prothymocytes (Thy-1-) to thymocytes (Thy-1+). From these results we propose the hypothesis that the differentiation of B lymphocytes proceeds through at least four distinct stages characterized by the following phenotypes: Ig-Ia-CR- leads to Ig+Ia-CR- leads to Ig+Ia+CR- leads to Ig+Ia+CR+.     

结核病小鼠T淋巴细胞亚群及其表达的四项细胞因子分析

目的 探讨T淋巴细胞(简称T细胞)表达穿孔素(PFN)、颗粒酶B(GzmB)、γ-干扰素(IFN-γ)、白细胞介素-2(IL-2)与结核免疫的关系.方法 60只MK小鼠按随机数字表法分成结核病组和健康对照组,每组30只.以CD3PerCP、CD4FTTC、CD8APC单抗标记T细胞亚群,以藻红蛋白标记PFN、GzmB、IFN-γ、IL-2单抗标记细胞因子,以流式细胞仪检测分析总的淋巴细胞、CD3+、CD4+、CD8+、CD4+CD8+;双阳(DP)T细胞计数和各亚群占淋巴细胞百分率,观察各T细胞亚群内表达PFN、GzmB、IFN-γ、IL-2的阳性细胞计数和各自占淋巴细胞百分率.采用t检验进行统计学分析.结果 (1)CD4+CD8+、DP T细胞均能不同程度地表达PFN、GzmB、IFN-γ、IL-2.PFN、GzmB的表达以CD8+T细胞占优势.IFN-γ、IL-2的表达以CD4+T细胞占优势.(2)T细胞亚群细胞计数结果与T细胞亚群占总淋巴细胞百分率结果,所反映的T细胞免疫变化趋势可能相似,也可能不同甚至相反.(3)两组间表达PFN的T细胞差别不明显,但结核病组表达GzmB的各个T细胞亚群计数和CD3+%、CD8+%、DP%高于对照组(t值为-3.72～4.13.均P<0.05).(4)结核病组表达IFN-γ的CD3+、CD4+T细胞计数高于对照组;但结核病组表达IL-2的CD8+、DP T细胞计数和CD3+%、CD4+%、CD8+%、DP%均低于对照组(t值为2.62～3.46,均P<0.05).结论 、CD,4+、CD8+、DPT细胞均能不同程度地表达PFN、GzmB、IFN-γ、IL-2;联合评价T细胞各亚群计数和其占淋巴细胞百分率更能判断免疫学状态.     

严重急性呼吸综合征患者淋巴细胞亚群的动态变化及意义

目的　了解成人严重急性呼吸综合征 (SARS)患者淋巴细胞亚群的改变对疾病的发生、发展及预后的影响。方法　依据卫生部颁发的传染性非典型肺炎临床诊断标准及预后将 2 0 6例SARS患者分为 3组 :即非重症组 13 3例、重症存活组 50例、重症死亡组 2 3例 ,用流式细胞仪进行淋巴细胞亚群CD4+、CD8+、CD19+、CD16+淋巴细胞的动态检测。建立数据库并对检测结果进行统计学分析。结果　SARS患者CD4+、CD8+、CD19+淋巴细胞计数均值分别是非重症组 >重症存活组 >重症死亡组 ,组间比较均P <0 .0 5。CD16+均值非重症组与重症存活组比较P >0 .0 5,两组与死亡组比较均P <0 .0 1。通过对CD4+、CD8+、CD19+、CD16+淋巴细胞计数动态观察 ,发现非重症组与重症存活组随病程CD4+、CD8+先下降后上升 ,CD19+随病程逐渐上升 ,CD 16+在发病早期有短暂的升高 ,然后波动在正常范围内。重症死亡组CD4+、CD8+、CD19+、CD16+在发病初期即处于较低水平 ,发病 15d后CD4+、CD8+、CD19+仍持续低水平 ,而CD16+随病程呈持续性降低。结论　成人SARS患者有明显的细胞免疫损伤 ,其淋巴细胞亚群的改变与临床分型及预后相关 ,对预后判断有一定的指导意义。SARS患者CD4+、CD8+淋巴细胞计数在发病初期是降低的 ,非重症组、重症存活组发病 9～15d是最     

Immunohistochemical analysis of granulomatous lung lesion in primary pulmonary cryptococcosis

Immunohistochemical analysis was performed in a case of pulmonary cryptococcosis that showed granulomatous pneumonia. The patient had no immunologic defects or other diseases. To cryostat sections, the immunocytes in granulomatous lesion were examined by application of monoclonal antibodies for T-lymphocytes, B-lymphocyte, macrophage series cells, lymphokines containing gamma interferon (gamma IFN), interleukin 1 (IL-1) and interleukin 2 (IL-2), and interleukin 2 receptor (IL-2R). CD2+ cells, CD3+ cells and CD4+ cells were in and around the granulomas. On the other hand, CD8+ cells were around the granulomas. In granulomatous lesions, the CD4/CD8 ratio was 2.0. Some T-lymphocytes were considered as activated lymphocytes showing OKDR+, IL-2+, gamma IFN+ or IL-2R+. The lymphoid cells that aggregated near the granulomas were B-lymphocytes showing CD21+, CD24+, s-IgD+, s-IgM+, OKDR+. According to these results they were mature B lymphocytes. Alveolar macrophages (AMs) were CD11+, CD36+, IL-1+, OKDR+. Epithelioid cells were CD4+, CD11+, CD36+, OKDR+, IL-1+, IL-2R+. CD1+ cells showing dendritic forms were scattered in granulomas. They were recognized to be Langerhans giant cells. These results suggest that in pulmonary cryptococcosis the formation of epithelioid cell granulomas is mainly induced by CD4+ cells (helper/inducer T-lymphocytes). Additionally, Langerhans giant cells and mature B lymphocytes may be related to humoral immunity in pulmonary cryptococcosis.     

Characterization of normal peripheral blood lymphocyte colony-forming cells: cell cycle status, surface markers, and cellular growth requirements

We performed a series of studies to further clarify the nature of lymphocyte colony-forming cells (CFC) from normal peripheral blood. Mononuclear cells were separated into E-rosette-enriched (E+) and E- rosette-depleted (E-) populations and cultured in methylcellulose with conditioned media and irradiated mononuclear cells. Linear plating relationships were obtained with plating efficiencies of 0.26% +/- .02% (mean +/- SE) for E+ CFC and 0.18% +/- .02% for E- CFC. Cells in E+ colonies were T lymphocytes and in E- colonies were B lymphocytes as determined by cell surface marker analysis. Using the thymidine suicide technique, approximately one-half of CFC were found to be in cycle at any moment, and plating efficiencies and cell cycle status of E+ CFC were not changed by preincubation with PHA in liquid culture for 48 hr. Using antibody complement-mediated cytotoxicity, E+ CFC were found to be T101+, OKT3+, and Ia-, while E- CFC were OKT3- and Ia+. Using monocyte-depleted populations obtained by sedimentation at unit gravity, lymphocyte colony growth was absent in monocyte-depleted fractions, and optimal growth occurred with 40% monocytes in culture. In contrast to some previous studies, we find that lymphocyte CFC originate from a small, cycling population of cells bearing mature T or B lymphocyte markers. Entry into cell division, however, does not confer colony-forming capacity on lymphocytes. Monocytes are critical to growth of E+ CFC, and cultures severely depleted of monocytes would not be expected to form colonies.     

Increased intrathecal immunoglobulin synthesis of both kappa and lambda types in patients with systemic lupus erythematosus and central nervous system involvement

The concentration of immunoglobulins in paired serum and cerebrospinal fluid (CSF) specimens from 15 patients with systemic lupus erythematosus (SLE) and central nervous system (CNS) involvement (CNS-SLE) were determined based on their light chain properties. Eight patients with SLE without CNS involvement and 20 patients with noninflammatory neurological diseases were also studied for comparison. We found that both of the CSF Ig-k (immunoglobulin kappa) and Ig-1 (immunoglobulin lambda) indices were significantly elevated, indicating the increased intrathecal immunoglobulin synthesis of both kappa and lambda types in patients with CNS-SLE. Moreover, the CSF Ig-k and Ig-1 indices correlated well with each other, and both indices were found to decrease remarkably when the CNS manifestations subsided after successful treatment. In 4 of 15 patients, intrathecal synthesis of free light chains in addition to Ig bound light chains seemed to be increased. These observations provide substantial evidence for polyclonal B lymphocyte activation within the CNS.     

大强度运动对大鼠脾脏淋巴细胞、巨噬细胞、T淋巴细胞亚群的影响

目的探讨大强度运动对大鼠脾脏淋巴细胞、巨噬细胞、T淋巴细胞亚的影响。方法40只SD大鼠按体重随机分为安静组(A组,n=10)、运动组(B组,n=30),在最后一次力竭运动后,将B组大鼠分为运动后即刻组(B 1组,n=10)、运动后12 h组(B 2组,n=10),运动后24 h组(B 3组,n=10)。A组不运动,B组大鼠进行为期9 w的大强度训练,末次训练后,A组、B 1组摘取脾脏,制作脾细胞悬液,噻唑蓝(MTT)法分别测T淋巴细胞增殖能力、B淋巴细胞增殖能力,流式细胞仪测CD4^+、CD8^+细胞数。中性红比色法测巨噬细胞吞噬能力。B 2组、B 3组分别在运动后12 h、运动后24 h按上述方法测试。结果与A组相比,B 1组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力显著降低,B 2组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD4^+/CD8^+显著降低,巨噬细胞吞噬能力差异无统计学意义,B 3组T淋巴细胞、B淋巴细胞增殖能力、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力差异无统计学意义;与B 1相比,B 2组、B 3组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+、CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力显著升高;与B 2相比,B 3组T淋巴细胞增殖、B淋巴细胞增殖、CD4^+均显著升高,CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力无显著差异。结论大强度运动后,大鼠脾脏、B淋巴细胞、T淋巴增殖能力降低、巨噬细胞吞噬能力降低、CD3^+、CD4^+、CD8^+、CD4^+/CD8^+降低,恢复期间逐步上升,其中CD8^+、CD4^+/CD8^+、巨噬细胞吞噬能力在恢复期12 h基本达到正常状态,T淋巴细胞增殖能力、B淋巴细胞增殖能力、CD4^+在恢复期24 h达到正常状态。     

Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: analysis with multiple breakpoint probes

Centrocytic lymphoma is a B-cell non-Hodgkin's lymphoma (NHL) composed of lymphocytes resembling cleaved follicular center cells (centrocytes). Previous studies have suggested an association between t(11;14) chromosomal translocations and bcl-1 rearrangement in centrocytic and related intermediate lymphocytic lymphomas. To further characterize the association between bcl-1 and centrocytic lymphoma, Southern blot analysis was performed on samples from 23 patients using four separate bcl-1 breakpoint probes spanning 63 kb of the chromosome 11 bcl-1 locus. Rearrangements were identified in six patients with the major translocation cluster (MTC) probe and in another six with probe p94PS, located about 24 kb 5' of MTC. Eleven of these 12 cases showed comigration of rearranged bcl-1 and Ig heavy chain-joining genes, consistent with the t(11;14) chromosomal translocation. No rearrangements were observed with the bcl-1 locus probes p210 or p11EH located 5' of p94PS, nor with bcl-2 or c-myc oncogene probes. No bcl-1 rearrangements were identified in B-cell follicular NHL (15), small noncleaved cell (Burkitt's and non-Burkitt's) NHL (8), T-cell NHL (4), multiple myeloma (14), and pre-B-cell acute lymphoblastic leukemia (9). One of 23 B-cell NHL of large cell type and one of 19 chronic lymphocytic leukemias or small lymphocytic NHL had MTC rearrangement. Thus, bcl-1 rearrangement occurred at MTC or p94PS in 12 of 23 centrocytic lymphomas (52%), confirming a nonrandom association and suggesting a pathogenetic role for the bcl-1 locus in this immunohistologic subtype of NHL.