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

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 Hum...

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Bibliographic Details
Published in:Current biology 2001-12, Vol.11 (24), p.1986-1989
Main Authors: Harless, Susan M., Lentz, Vicky M., Sah, Alex P., Hsu, Benjamin L., Clise-Dwyer, Karen, Hilbert, David M., Hayes, Colleen E., Cancro, Michael P.
Format: Article
Language:English
Subjects:
Animals
B-Cell Activation Factor Receptor
B-Lymphocytes - cytology
Bcmd protein
BlyS protein
BR3 protein
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
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Summary: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.
ISSN:0960-9822
1879-0445
DOI:10.1016/S0960-9822(01)00598-X