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.
authors.affiliation: Section of Immunobiology, Department of Laboratory Medicine, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. mlevine@biomed.med.yale.edu
authors.forename: M H
authors.initials: MH
authors.lastname: Levine
authors.forename: A M
authors.initials: AM
authors.lastname: Haberman
authors.forename: D B
authors.initials: DB
authors.lastname: Sant'Angelo
authors.forename: L G
authors.initials: LG
authors.lastname: Hannum
authors.forename: M P
authors.initials: MP
authors.lastname: Cancro
authors.forename: C A
authors.initials: CA
authors.lastname: Janeway
authors.forename: M J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016923:Cell Death; D002454:Cell Differentiation; D003001:Cloning, Molecular; D005434:Flow Cytometry; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013269:Stochastic Processes
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell