Frequent occurrence of identical heavy and light chain Ig rearrangements |
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Authors: | Seidl, KJ MacKenzie, JD Wang, D Kantor, AB Kabat, EA Herzenberg, LA Herzenberg, LA |
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Affiliation: | Department of Genetics, Beckman Center B007, Stanford University School of Medicine, CA 94305-5125, USA. |
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Abstract: | Single-cell PCR analyses of expressed Ig H and L chain sequences presentedhere show that certain rearrangements occur repeatedly and account for amajor segment of the well-studied repertoire of B-1 cell autoantibodiesthat mediate the lysis of bromelain-treated mouse erythrocytes, i.e.antibodies reactive with phosphatldyicholine (PtC). We repeatedly isolatedat least 10 different types of VH region rearrangements, involving threedistinct germline genes, among FACS- sorted PtC-binding B-1 cells fromthree strains of mice (C57BL/6J, BALB/c and C.B-17). The predominantrearrangement, VH11-DSP-JH1 (VH11 type 1), has been previously found inanti-PtC hybridomas in several studies. We show that within each of sixmice from two strains (C57BL/6J and BALB/c), unique instances of IgH/IgLpairing arose either from different B cell progenitors prior to IgHrearrangement or from pre-B cells which expanded after IgH rearrangementbut prior to IgL rearrangement. Together with other recurrentrearrangements described here, our findings demonstrate that clonalexpansion of mature B cells cannot account for all repeated rearrangements.As suggested by initial studies of dominant idiotype expression, thesefindings confirm that clonal expansion is only one of the mechanismscontributing to the establishment of recurrent rearrangements. |
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