Laboratory for Mucosal Immunity, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):722-7. doi: 10.1073/pnas.1014697108. Epub 2010 Dec 27.
B1 cells represent a distinct subset of B cells that produce most of the natural serum IgM and much of the gut IgA and function as an important component of early immune responses to pathogens. The development of B1 cells depends on the nuclear factor of activated T cells c1 (NFATc1), a transcription factor abundantly expressed by B1 cells but not by conventional B2 cells. However, the factors that regulate the expression of NFATc1 in B1 cells remain unknown. Here we show that a vitamin A-deficient diet results in reduction of NFATc1 expression in B1 cells and almost complete loss of the B1 cell compartment. As a consequence, vitamin A-deficient mice have reduced serum IgM and are unable to mount T cell-independent antibody responses against bacterial antigens. We demonstrate that injection of all-trans retinoic acid induces the expression of NFATc1, particularly from the constitutive P2 promoter, and leads to the increase of the B1 cells. Thus, the retinoic acid-dependent pathway is critical for regulating NFATc1 expression and for maintenance of the natural memory B cell compartment.
B1 细胞是 B 细胞的一个独特亚群，它们产生大部分天然血清 IgM 和大部分肠道 IgA，并作为对病原体早期免疫反应的重要组成部分发挥作用。B1 细胞的发育依赖于激活 T 细胞核因子 c1（NFATc1），这是一种在 B1 细胞中大量表达而在常规 B2 细胞中不表达的转录因子。然而，调节 B1 细胞中 NFATc1 表达的因素仍不清楚。在这里，我们表明，维生素 A 缺乏饮食导致 B1 细胞中 NFATc1 表达减少，几乎完全丧失 B1 细胞区室。结果，维生素 A 缺乏的小鼠血清 IgM 减少，并且无法对细菌抗原产生 T 细胞非依赖性抗体反应。我们证明，全反式视黄酸的注射诱导 NFATc1 的表达，特别是从组成性 P2 启动子，导致 B1 细胞的增加。因此，视黄酸依赖性途径对于调节 NFATc1 的表达和维持天然记忆 B 细胞区室至关重要。
