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

Curr Biol. 2001 Dec 11;11(24):1986-9. doi: 10.1016/s0960-9822(01)00598-x.


Striking cell losses occur during late B lymphocyte maturation, reflecting BcR-mediated selection coupled with requisites for viability promoting signals. 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 as well as the B lineage-specific expression of BLyS receptors. Our analyses of the B cell-deficient A/WySnJ mouse have established Bcmd as a gene controlling follicular B cell life span, and recent reports show Bcmd encodes a novel BLyS receptor. 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 x BALB/c)F(1) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / cytology*
  • Cell Survival / physiology
  • Heterozygote
  • Lymphocyte Count*
  • Membrane Proteins*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction* / physiology*


  • B-Cell Activation Factor Receptor
  • BLyS receptor
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf13c protein, mouse