LBAI, UMR1227, Univ Brest, Inserm, and CHU de Brest, Brest, France.
Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, 80045, USA.
Nat Commun. 2024 Sep 12;15(1):7982. doi: 10.1038/s41467-024-52224-6.
Precise regulation of B cell differentiation is essential for an effective adaptive immune response. Here, we show that B cell development in mice with B cell-specific Maf deletion is unaffected, but marginal zone B cells, germinal centre B cells, and plasmablasts are significantly more frequent in the spleen of naive Maf-deficient mice compared to wild type controls. In the context of a T cell-dependent immunization, Maf deletion causes increased proliferation of germinal centre B cells and extrafollicular plasmablasts. This is accompanied by higher production of antigen-specific IgG1 antibodies with minimal modification of early memory B cells, but a reduction in plasma cell numbers. Single-cell RNA sequencing shows upregulation of genes associated with DNA replication and cell cycle progression, confirming the role of Maf in cell proliferation. Subsequent pathway analysis reveals that Maf influences cellular metabolism, transporter activity, and mitochondrial proteins, which have been implicated in controlling the germinal centre reaction. In summary, our findings demonstrate that Maf acts intrinsically in B cells as a negative regulator of late B cell differentiation, plasmablast proliferation and germinal centre B cell formation.
精确调控 B 细胞分化对于有效的适应性免疫反应至关重要。在这里，我们发现 B 细胞特异性 Maf 缺失的小鼠中 B 细胞的发育不受影响，但与野生型对照相比，幼稚 Maf 缺陷型小鼠脾脏中的边缘区 B 细胞、生发中心 B 细胞和浆母细胞明显更为频繁。在 T 细胞依赖性免疫接种的情况下，Maf 缺失导致生发中心 B 细胞和滤泡外浆母细胞的增殖增加。这伴随着抗原特异性 IgG1 抗体的产生增加，早期记忆 B 细胞的修饰最小，但浆细胞数量减少。单细胞 RNA 测序显示与 DNA 复制和细胞周期进程相关的基因上调，证实了 Maf 在细胞增殖中的作用。随后的通路分析表明，Maf 影响细胞代谢、转运蛋白活性和线粒体蛋白，这些蛋白已被证明参与控制生发中心反应。总之，我们的研究结果表明，Maf 在 B 细胞中作为晚期 B 细胞分化、浆母细胞增殖和生发中心 B 细胞形成的负调节剂发挥内在作用。
