Whitmire Jason K, Asano Mary S, Kaech Susan M, Sarkar Surojit, Hannum Lynn G, Shlomchik Mark J, Ahmed Rafi
Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 2009 Feb 15;182(4):1868-76. doi: 10.4049/jimmunol.0802501.
B cells can influence T cell responses by directly presenting Ag or by secreting Ab that binds to Ag to form immunogenic complexes. Conflicting evidence suggests that persisting Ag-Ab complexes propagate long-term T cell memory; yet, other data indicate that memory cells can survive without specific Ag or MHC. In this study, the roles of B cells and Ag-Ab complexes in T cell responses to lymphocytic choriomeningitis virus (LCMV) infection were investigated using B cell-deficient or B cell-competent mice. Despite normal lymphocyte expansion after acute infection, B cell-deficient mice rapidly lost CD4(+) T cell memory, but not CD8(+) T cell memory, during the contraction phase. To determine whether Ag-Ab complexes sustain CD4(+) T cell memory, T cell responses were followed in B cell-transgenic (mIg-Tg) mice that have B cells but neither LCMV-specific Ab nor LCMV-immune complex deposition. In contrast to B cell-deficient mice, mIg-Tg mice retained functional Th cell memory, indicating that B cells selectively preserve CD4(+) T cell memory independently of immune complex formation. An in vivo consequence of losing CD4(+) T cell memory was that B cell-deficient mice were unable to resolve chronic virus infection. These data implicate a B cell function other than Ab production that induces long-term protective immunity.
B细胞可通过直接呈递抗原或分泌与抗原结合形成免疫原性复合物的抗体来影响T细胞反应。相互矛盾的证据表明，持续存在的抗原-抗体复合物可促进长期T细胞记忆；然而，其他数据表明记忆细胞在没有特异性抗原或主要组织相容性复合体（MHC）的情况下也能存活。在本研究中，利用B细胞缺陷或有B细胞功能的小鼠，研究了B细胞和抗原-抗体复合物在针对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的T细胞反应中的作用。尽管急性感染后淋巴细胞正常扩增，但在收缩期，B细胞缺陷小鼠迅速丧失CD4(+) T细胞记忆，但未丧失CD8(+) T细胞记忆。为了确定抗原-抗体复合物是否维持CD4(+) T细胞记忆，对有B细胞但既没有LCMV特异性抗体也没有LCMV免疫复合物沉积的B细胞转基因（mIg-Tg）小鼠的T细胞反应进行了跟踪。与B细胞缺陷小鼠不同，mIg-Tg小鼠保留了功能性辅助性T细胞记忆，表明B细胞可独立于免疫复合物形成选择性地保留CD4(+) T细胞记忆。丧失CD4(+) T细胞记忆的一个体内后果是，B细胞缺陷小鼠无法清除慢性病毒感染。这些数据表明，除了产生抗体外，B细胞还有诱导长期保护性免疫的功能。
