Fcgamma RIIb: differential expression and functions in B cell subsets

AMEZCUA VESELY MC; BERMEJO D; CAUTIVO, KM; MONTES CL; KALERGIS A; ACOSTA RODRIGUEZ EV; GRUPPI A

Buenos Aires

Congreso; First French–Argentine Immunology Congress. LVIII reunión Anual de la Sociedad Argentina de Inmunologia.; 2010

SAI

FcgammaRIIb (FcR) is the only receptor for the IgG Fc portion expressed on B cells. FcR crosslinking induces apoptosis of plasma and splenic B cells. Our aim was to evaluate the expression profile of FcR on different B cell subsets and its relationship with cell survival and the ability to produce antibodies (Abs). Phenotypic analysis showed that among all B cell subsets, peritoneal B1 cells (pB1) express the highest levels of FcR. Accordingly, pB1 are much more susceptible to apoptosis induced via FcR than splenic B2 cells (sB2). To address the role of FcR in the homeostasis of the different B cell subsets, we studied FcR knockout (KO) mice. We found higher number of pB1 and similar number sB2 in comparison with wild type (WT) mice. pB1 from KO mice showed in vivo the same level of BrdU incorporation than pB1 from WT, indicating that the increase in the number of pB1 in KO mice is not a consequence of an accelerated proliferation rate. We also observed that stimuli that induce B cells differentiation to Ab-secreting-cell (ASC), such as LPS or CpG, upregulated FcR expression to levels that were similar in all B cell subsets.  Consequently, CpG-stimulated pB1 and sB2 were equally susceptible to FcR-induced apoptosis. To evaluate the association between high levels of FcR expression and the ability of cells to secrete Abs, we determined by ELIspot the frequency of ASC in FcRhigh CD138+ and FcRhigh CD138- cells sorted from CpG-stimulated pB1 and sB2 and FcRlow CD138neg cells sorted from unstimulated pB1 and sB2. We observed similar frequencies of IgM- and IgG- ASC in stimulated pB1 and sB2 cells that expressed high levels of FcR independently on the expression of CD138 while the unstimulated FcRlow cell population contained few or none ASC. This result indicated that the up-regulation of FcR on B cell subsets correlated with the acquisition of the ability to secrete Abs, postulating FcR as a new marker to identify plasmablast. Altogether our findings indicated that FcR is a key receptor controlling pB1 cell survival in steady-state conditions. Under stimulatory conditions, FcR was able to trigger apoptosis in all the B cell subsets in a mechanism highly dependent on the upregulation of this receptor. These results suggested that there may be a threshold in FcR expression beyond which all B cells become equally susceptible to FcR-mediated apoptosis.