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

MH Levine, AM Haberman… - Proceedings of the …, 2000 - National Acad Sciences
MH Levine, AM Haberman, DB Sant'Angelo, LG Hannum, MP Cancro, CA Janeway Jr…
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
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 …
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.
National Acad Sciences