[PDF][PDF] Competition for BLyS-mediated signaling through Bcmd/BR3 regulates peripheral B lymphocyte numbers

SM Harless, VM Lentz, AP Sah, BL Hsu, K Clise-Dwyer… - Current Biology, 2001 - cell.com
SM Harless, VM Lentz, AP Sah, BL Hsu, K Clise-Dwyer, DM Hilbert, CE Hayes, MP Cancro
Current Biology, 2001cell.com
Striking cell losses occur during late B lymphocyte maturation [1–3], reflecting BcR-mediated
selection coupled with requisites for viability promoting signals [4–11]. How selection and
survival cues are integrated remains unclear, but a key role for B lymphocyte stimulator
(BLyS TM; trademark of Human Genome Sciences, Inc.) is suggested by its marked effects
on B cell numbers and autoantibody formation [12–18] as well as the B lineage-specific
expression of BLyS receptors [19–23]. Our analyses of the B cell-deficient A/WySnJ mouse …
Abstract
Striking cell losses occur during late B lymphocyte maturation [1–3], reflecting BcR-mediated selection coupled with requisites for viability promoting signals [4–11]. How selection and survival cues are integrated remains unclear, but a key role for B lymphocyte stimulator (BLySTM; trademark of Human Genome Sciences, Inc.) is suggested by its marked effects on B cell numbers and autoantibody formation [12–18] as well as the B lineage-specific expression of BLyS receptors [19–23]. Our analyses of the B cell-deficient A/WySnJ mouse have established Bcmd as a gene controlling follicular B cell life span [24–27], and recent reports show Bcmd encodes a novel BLyS receptor [23, 28, 29]. Here we show that A/WySnJ B cells are unresponsive to BLyS, affording interrogation of how Bcmd influences B cell homeostasis. Mixed marrow chimeras indicate A/WySnJ peripheral B cells compete poorly for peripheral survival. Moreover, in vivo BrdU labeling shows that (A/WySnJ × BALB/c)F1 B cells have an intermediate but uniform life span, indicating viability requires continuous signaling via this pathway. Together, these findings establish the BLyS/Bcmd pathway as a dominant mediator of B cell survival, suggesting competition for BLyS/Bcmd signals regulates follicular B cell numbers.
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