| First Author | Mayne CG | Year | 2009 |
| Journal | Mol Immunol | Volume | 47 |
| Issue | 2-3 | Pages | 590-9 |
| PubMed ID | 19815275 | Mgi Jnum | J:155362 |
| Mgi Id | MGI:4413545 | Doi | 10.1016/j.molimm.2009.09.010 |
| Citation | Mayne CG, et al. (2009) Murine BAFF-receptor residues 168-175 are essential for optimal CD21/35 expression but dispensable for B cell survival. Mol Immunol 47(2-3):590-9 |
| abstractText | BAFF-R (B cell-activating factor belonging to the tumor necrosis factor family receptor) regulates B lymphocyte survival, maturation, homeostasis, and self-tolerance through signaling mechanisms that are not completely understood. A spontaneous BAFF-R mutation, Bcmd-1, disrupts BAFF-R signaling. However, it is not clear why the Bcmd-1-encoded BAFF-R fails to adequately support B cell survival, optimal CD21/35 expression, and B-cell tolerance to dsDNA, since it is 95% identical to the wild-type (wt) BAFF-R and retains the only known signaling motif. A retrotransposon insertion in A/WySnJ strain mice generated the Bcmd-1 allele, replacing the eight C-terminal BAFF-R residues with 21 retrotransposon-encoded residues. New data reported here show that the displaced residues, previously thought to have no signaling role, are essential for optimal CD21/35 expression but contribute little to B cell survival signaling. Analysis of wt Baffr or Bcmd-1 homozygous (A/WySnJ X B6.BCL2)F2 mice confirmed that BCL2 complemented Bcmd-1 for B cell survival but not CD21/35 expression. Through in vivo retroviral transduction experiments, we show that Baffr complemented Bcmd-1 for B cell survival but not CD21/35 expression, whereas the BaffrDelta103-175 deletion mutant lacking the BAFF-R cytoplasmic domain failed to support these functions. Importantly, we show that the BaffrDelta168-175 deletion mutant lacking the retrotransposon-displaced residues, and a BaffrT170A mutant lacking a critical threonine, supported B cell survival but failed to support optimal CD21/35 expression. These data provide the first evidence for a possible bifurcation at the receptor level in the BAFF-R signaling pathway. We suggest that discrete BAFF-R cytoplasmic domains may interact with distinct downstream pathways to provide fine control over B cell survival, maturation, and tolerance induction. |
