A B-cell receptor-specific selection step governs immature to mature B cell differentiation Journal Article


Authors: Levine, M. H.; Haberman, A. M.; Sant'angelo, D. B.; Hannum, L. G.; Cancro, M. P.; Janeway, C. A. Jr; Shlomchik, M. J.
Article Title: A B-cell receptor-specific selection step governs immature to mature B cell differentiation
Abstract: Seventy percent of peripheral immature conventional (B2) B cells fail to develop into mature B cells. The nature of this cell loss has not been characterized; the process that governs which immature B cells develop into long-lived peripheral B cells could be either stochastic or selective. Here, we demonstrate that this step is in fact selective, in that the fate of an immature B cell is highly dependent on its Ig receptor specificity. A significant skewing of the B cell receptor repertoire occurs by the time cells enter the mature B cell fraction, which indicates that there is selection of only a minority of immature B cells to become mature B cells. Because only a few heavy-light chain pairs are enhanced of the diverse available repertoire, we favor the idea that selection is positive for these few heavy-light chain pairs rather than negative against nearly all others. Because most immature B cells are lost at this transition, this putative positive selection event is likely to be a major force shaping the mature B cell receptor repertoire available for adaptive immune responses.
Keywords: controlled study; sequence analysis; nonhuman; flow cytometry; animal cell; mouse; animals; mice; cell death; gene amplification; cell maturation; spleen; cell differentiation; transgenic mouse; animalia; mus musculus; b-lymphocytes; mice, transgenic; molecular cloning; cloning, molecular; immunoglobulin heavy chain; immunoglobulin heavy chains; molecular sequence data; nucleotide sequence; immunoglobulin light chain; immunoglobulin light chains; stochastic processes; immunologic memory; cell selection; b lymphocyte differentiation; immunoglobulin m; receptors, antigen, b-cell; immunoglobulin receptor; b lymphocyte receptor; cell loss; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 97
Issue: 6
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2000-03-14
Start Page: 2743
End Page: 2748
Language: English
DOI: 10.1073/pnas.050552997
PUBMED: 10688906
PROVIDER: scopus
PMCID: PMC16000
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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