Bmpr1a’nın Plazma Hücrelerinin Gelişimine Etkisinin ve Germinal Merkez Dinamiklerindeki Öneminin Araştırılması

Abstract

The bone morphogenetic protein receptor 1A (BMPR1A) signaling pathway regulates self-renewal, proliferation, and differentiation in embryonic and adult stem cells as well as in adult lymphoid cells. Here, using transgenic mice with conditional deletion of Bmpr1a in B cell and novel Bmpr1a.IRES.EGFP reporter mice, we demonstrate that BMPR1A signaling regulates germinal center dynamics and establishment of bone marrow plasma cell compartment. In C57Bl/6J (B6) mice, Bmpr1a mRNA was upregulated among germinal center B cells (GCBC), memory B cells (MBC) and bone marrow plasma cells (BMPC). In mice with B-cell specific Bmpr1a deficiency, the size of the GCBC compartment were reduced to 77 % that of wildtype control mice and the size of IgG1+ BMPC compartment were diminished to 34 % that of controls. Similarly, high affinity IgG1 and moderate affinity IgM antibodies in serum were decreased. Despite the importance of BMPR1A in T-dependent response, T-independent immune response didn’t require the BMPR1A signaling. The class switch mechanism was also not affected in the absence of Bmpr1a. Interestingly, Bmpr1a expression was unique to a subset of germinal center B cells which has high Xbp1, IRF-4, and Blimp1 expression. Bmpr1a.eGFP mice studies showed that the expression of Bmpr1a in GCBC increases over time and Bmpr1a is upregulated in a subset of BMPC population. Overall, this study shows that BMPR1A signaling plays a role in modulating the germinal center dynamics and the formation of T-dependent bone-marrow plasma cells.