美国马萨诸塞大学医学院Andrea Reboldi课题组近日取得一项新成果。他们研究发现抗原受体信号传导和细胞死亡抵抗控制肠道体液反应。该项研究成果发表在2023年9月14日出版的《免疫》上。

研究人员表明，在派尔集合淋巴结（PPs）生发中心（GC）反应期间，B细胞适应性和肠道归巢浆细胞（PC）的产生需要免疫球蛋白A（IgA）B细胞受体（BCR）。研究证明IgA BCR驱动小鼠和人类B细胞中细胞内信号传导增强，因此，IgA⁺ B细胞获得了更强的正向选择刺激。

从机制上讲，IgA BCR信号与Fas介导的死亡相抵消，这可能挽救低亲和力B细胞以促进对共生细菌的广泛体液反应。该研究结果揭示了与BCR信号传导、B细胞命运和抗体产生位置有关的另一种机制，这对肠道抗原识别如何重塑体液免疫具有影响。

据了解，免疫球蛋白A维持肠道共生菌群，同时防止生态失衡。肠道微生物诱导产生的IgA可同时与多种不同的共生抗原结合。然而，B细胞产生针对肠道微生物组IgA的确切机制仍然未知。

附：英文原文

Title: Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation

Author: Fiona Raso, Shuozhi Liu, Mikala J. Simpson, Gregory M. Barton, Christian T. Mayer, Mridu Acharya, Jagan R. Muppidi, Ann Marshak-Rothstein, Andrea Reboldi

Issue&Volume:

Abstract: Immunoglobulin A (IgA) maintains commensal communities in the intestine while preventingdysbiosis. IgA generated against intestinal microbes assures the simultaneous bindingto multiple, diverse commensal-derived antigens. However, the exact mechanisms bywhich B cells mount broadly reactive IgA to the gut microbiome remains elusive. Here,we have shown that IgA B cell receptor (BCR) is required for B cell fitness duringthe germinal center (GC) reaction in Peyer’s patches (PPs) and for generation of gut-homingplasma cells (PCs). We demonstrate that IgA BCR drove heightened intracellular signalingin mouse and human B cells, and as a consequence, IgA+ B cells received stronger positive selection cues. Mechanistically, IgA BCR signalingoffset Fas-mediated death, possibly rescuing low-affinity B cells to promote a broadhumoral response to commensals. Our findings reveal an additional mechanism linkingBCR signaling, B cell fate, and antibody production location, which have implicationsfor how intestinal antigen recognition shapes humoral immunity.

DOI: 10.1016/j.immuni.2023.08.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00374-6