A B-Cell Receptor-Specific Selection Step Governs Immature to Mature B Cell Differentiation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 6; pp. 2743 - 2748
• Main Authors: Levine, Matthew H, Haberman, Ann M, Sant'Angelo, Derek B, Hannum, Lynn G
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 14.03.2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: AB-cell receptor; Animals; Antigens; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Biological Sciences; Bone marrow; Cell Death; Cell Differentiation; Cell lines; Cells; Cellular biology; Cloning, Molecular; Family members; Flow Cytometry; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Light Chains - immunology; Immunoglobulin M - immunology; Immunologic Memory; Immunology; Mice; Mice, Transgenic; Molecular Sequence Data; Negative selection; Polymerase chain reaction; Positive selection; Receptors; Receptors, Antigen, B-Cell - physiology; Spleen - cytology; Stochastic Processes; Transgenic animals
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.050552997

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.