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 |