Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.
Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
J Exp Med. 2020 Nov 2;217(11). doi: 10.1084/jem.20200147.
B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the IghPax5/+ mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young IghPax5/+ mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in IghPax5/+ plasma cells. While IgM and IgA secretion by IghPax5/+ plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.
B 细胞和浆细胞命运由不同的转录网络控制，例如 B 细胞身份因子 Pax5 和浆细胞调节因子 Blimp1 的相互排斥表达和交叉拮抗。有人假设 Blimp1 对 Pax5 的抑制对于浆细胞发育是必不可少的。在这里，我们通过分析表达免疫球蛋白重链基因座上 Pax5 基因的 IghPax5/+ 小鼠来挑战这一假设。尽管 Pax5 表达水平很高，但在年轻的 IghPax5/+ 小鼠中，浆细胞在稳态和免疫时能有效地发育，而在老年小鼠中其数量适度减少。尽管 Pax5 显著下调了浆细胞的表达程序，但关键的浆细胞调节因子在 IghPax5/+ 浆细胞中正常表达。虽然 IghPax5/+ 浆细胞的 IgM 和 IgA 分泌正常，但 IgG 分泌略有减少。因此，尽管 Pax5 的抑制对于产生最佳 IgG 和积累长寿浆细胞是必需的，但对于强壮的浆细胞发育和抗体分泌并非必不可少。
