Quemeneur Laurence, Angeli Veronique, Chopin Michael, Jessberger Rolf
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Blood. 2008 Mar 1;111(5):2714-24. doi: 10.1182/blood-2007-07-102822. Epub 2007 Dec 19.
Germinal centers (GCs) are lymphoid tissue structures central to the generation of long-lived, high-affinity, antibody-forming B cells. However, induction, maintenance, and regulation of GCs are not sufficiently understood. The F-actin-binding, Rac-interacting protein SWAP-70 is strongly expressed in activated B cells like those in B follicles. Recent work suggests that SWAP-70 is involved in B-cell activation, migration, and homing. Therefore, we investigated the role of SWAP-70 in the T-dependent immune response, in GC formation, and in differentiation into plasma and memory B cells. Compared with wt, sheep red blood cell (SRBC)-, or NP-KLH-immunized SWAP-70(-/-) mice have strongly reduced numbers of GCs and GC-specific B cells. However, SWAP-70(-/-) NP-specific B cells accumulate outside of the B follicles, and SWAP-70(-/-) mice show more plasma cells in the red pulp and in the bone marrow, and increased NP-specific Ig and antibody-forming B cells. Yet the memory response is impaired. Thus, SWAP-70 deficiency uncouples GC formation from T-dependent antibody and long-lived plasma cell production and causes extrafollicular generation of high-affinity plasma cells, but does not adequately support the memory response.
生发中心（GCs）是淋巴组织结构，对于产生长寿、高亲和力、形成抗体的B细胞至关重要。然而，人们对GCs的诱导、维持和调控了解还不够充分。F-肌动蛋白结合、Rac相互作用蛋白SWAP-70在活化B细胞（如B滤泡中的细胞）中强烈表达。最近的研究表明，SWAP-70参与B细胞的活化、迁移和归巢。因此，我们研究了SWAP-70在T细胞依赖性免疫反应、GC形成以及分化为浆细胞和记忆B细胞中的作用。与野生型、经绵羊红细胞（SRBC）或NP-KLH免疫的SWAP-70（-/-）小鼠相比，GCs和GC特异性B细胞数量大幅减少。然而，SWAP-70（-/-）NP特异性B细胞在B滤泡外积聚，并且SWAP-70（-/-）小鼠在红髓和骨髓中显示出更多浆细胞，以及NP特异性Ig和形成抗体的B细胞增加。然而，记忆反应受损。因此，SWAP-70缺陷使GC形成与T细胞依赖性抗体和长寿浆细胞产生脱钩，并导致滤泡外产生高亲和力浆细胞，但不能充分支持记忆反应。
