Categorical selection of the antibody repertoire in splenic B cells.
In the bone marrow, the passage of developing B cells through critical checkpoints of differentiation is associated with a reduction of specific categories of CDR3 of the Ig heavy chain (CDR-H3), particularly those with excessive hydrophobic or charged amino acids and those with a length of eight or fewer residues. To gain insight into the role of CDR-H3 content in the development of B cells in the spleen, we compared the sequences of V(H)7183DJCmu transcripts from sorted transitional T1, marginal zone, and follicular B cell subsets to those expressed by immature IgM(+)IgD(-) and mature IgM(lo)IgD(hi) B cells in the bone marrow. Although differences in V(H) utilization were noted, the T1 CDR-H3 repertoire showed extensive similarity to that of immature bone marrow B cells, and the follicular CDR-H3 repertoire most resembled that of mature bone marrow B cells. Unlike the splenic follicular and bone marrow mature B cell CDR-H3 repertoires, the marginal zone B cell CDR-H3 repertoire retained both short and highly charged amino acid motifs, including those with two arginines. Our findings suggest that antigen binding sites containing specific categories of CDR-H3 sequence content may inhibit, permit, or even facilitate passage of the host B cell through critical checkpoints in peripheral as well as central development.
Schelonka
Robert L
RL
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233-1530, USA. rschelon@uab.edu
Tanner
Jason
J
Zhuang
Yingxin
Y
Gartland
G Larry
GL
Zemlin
Michael
M
Schroeder
Harry W
HW
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000145:classification; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region