Frequent occurrence of identical heavy and light chain Ig rearrangements.
Single-cell PCR analyses of expressed Ig H and L chain sequences presented here show that certain rearrangements occur repeatedly and account for a major segment of the well-studied repertoire of B-1 cell autoantibodies that mediate the lysis of bromelain-treated mouse erythrocytes, i.e. antibodies reactive with phosphatldyicholine (PtC). We repeatedly isolated at least 10 different types of VH region rearrangements, involving three distinct germline genes, among FACS-sorted PtC-binding B-1 cells from three strains of mice (C57BL/6J, BALB/c and C.B-17). The predominant rearrangement, VH11-DSP-JH1 (VH11 type 1), has been previously found in anti-PtC hybridomas in several studies. We show that within each of six mice from two strains (C57BL/6J and BALB/c), unique instances of IgH/IgL pairing arose either from different B cell progenitors prior to IgH rearrangement or from pre-B cells which expanded after IgH rearrangement but prior to IgL rearrangement. Together with other recurrent rearrangements described here, our findings demonstrate that clonal expansion of mature B cells cannot account for all repeated rearrangements. As suggested by initial studies of dominant idiotype expression, these findings confirm that clonal expansion is only one of the mechanisms contributing to the establishment of recurrent rearrangements.
Seidl
K J
KJ
Department of Genetics, Beckman Center B007, Stanford University School of Medicine, CA 94305-5125, USA.
MacKenzie
J D
JD
Wang
D
D
Kantor
A B
AB
Kabat
E A
EA
Herzenberg
L A
LA
Herzenberg
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001666:Binding Sites, Antibody; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology*; D005854:Germ Cells / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D010713:Phosphatidylcholines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013194:Staining and Labeling
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D008081:Liposomes; D010713:Phosphatidylcholines; D011947:Receptors, Antigen, B-Cell