Menard Laurence C, Minns Laurie A, Darche Sylvie, Mielcarz Daniel W, Foureau David M, Roos David, Dzierszinski Florence, Kasper Lloyd H, Buzoni-Gatel Dominique
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
J Immunol. 2007 Oct 1;179(7):4857-66. doi: 10.4049/jimmunol.179.7.4857.
Aside from being the precursors of the Ab-secreting cells, B cells are engaged in other immune functions such as Ag presentation to T cells or cytokine production. These functions may contribute to the pathogenic role of B cells in a wide range of autoimmune diseases. We demonstrate that B cells acquire the capacity to amplify IFN-gamma production by CD4 and CD8 T cells during the course of the Th1 inflammatory response to Toxoplasma gondii infection. Using the two following different strategies, we observed that B cells from T. gondii-infected mice, but not from naive mice, induce higher IFN-gamma expression by splenic host T cells: 1) reconstitution of B cell-deficient mice with B cells expressing an alloantigen different from the recipients, and 2) adoptive transfer of B and T cells into RAG-/- mice. In vitro assays allowing the physical separation of T and B cells demonstrate that Ag-primed B cells enhance IFN-gamma production by T cells in a contact-dependent fashion. Using an OVA-transgenic strain of T. gondii and OVA-specific CD4 T cells, we observed that the proinflammatory effect of B cells is neither Ag specific nor requires MHCII expression. However, TNF-alpha expressed on the surface of B cells appears to mediate in part the up-regulation of IFN-gamma by the effector T cells.
除了作为分泌抗体细胞的前体之外，B细胞还参与其他免疫功能，如向T细胞呈递抗原或产生细胞因子。这些功能可能在多种自身免疫性疾病中促成B细胞的致病作用。我们证明，在对刚地弓形虫感染的Th1炎症反应过程中，B细胞获得了增强CD4和CD8 T细胞产生γ干扰素的能力。通过以下两种不同策略，我们观察到，来自刚地弓形虫感染小鼠而非未感染小鼠的B细胞，可诱导脾脏宿主T细胞产生更高水平的γ干扰素：1）用表达与受体不同的同种异体抗原的B细胞重建B细胞缺陷小鼠；2）将B细胞和T细胞过继转移到RAG-/-小鼠体内。体外实验允许对T细胞和B细胞进行物理分离，结果表明，经抗原致敏的B细胞以接触依赖的方式增强T细胞产生γ干扰素的能力。利用刚地弓形虫的OVA转基因株和OVA特异性CD4 T细胞，我们观察到B细胞的促炎作用既不是抗原特异性的，也不依赖MHCII表达。然而，B细胞表面表达的肿瘤坏死因子-α似乎部分介导了效应T细胞对γ干扰素的上调作用。
