A B-cell receptor-specific selection step governs immature to mature B cell differentiation.
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.
Levine
M H
MH
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
Haberman
A M
AM
Sant'Angelo
D B
DB
Hannum
L G
LG
Cancro
M P
MP
Janeway
C A
CA
Shlomchik
M J
MJ
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
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell