CTLA-4 expression by B-1a B cells is essential for immune tolerance

• DOI: 10.1038/s41467-020-20874-x
• Publication Date: 2021-01-22T11:29:32Z
• Authors: Yang Yang; Xiao Li; Zhihai Ma; Chunlin Wang; Qunying Yang; Miranda Byrne-Steele; Rongjian Hong; Qing Min; Gao Zhou; Yong Cheng; Guang Qin; Justin V. Youngyu...; James B. Wing; Shimon Sakaguchi; Christian Toonstra; Lai-Xi Wang; Jose G. Vilches-M...; Denong Wang; Michael P. Snyder; Ji-Yang Wang; Jian Han; Leonore A. Herzen...
• Keywords: B-1 cell; Regulatory B cells; CTLA-4; Naive B cell

Abstract CTLA-4 is an important regulator of T-cell function. Here, we report that expression this immune-regulator in mouse B-1a cells has a critical function maintaining self-tolerance by regulating these early-developing B express repertoire enriched for auto-reactivity. Selective deletion from results mice spontaneously develop autoantibodies, T follicular helper (Tfh) and germinal centers (GCs) the spleen, autoimmune pathology later life. This impaired immune homeostasis cell dysfunction upon loss CTLA-4. Therefore, CTLA-4-deficient up-regulate epigenetic transcriptional activation programs show increased self-replenishment. These activated further internalize surface IgM, differentiate into antigen-presenting and, when reconstituted normal IgH-allotype congenic recipient mice, induce GCs Tfh expressing highly selected repertoire. findings regulation crucial immune-regulatory mechanism.