Dubois Cauwelaert Natasha, Baldwin Susan L, Orr Mark T, Desbien Anthony L, Gage Emily, Hofmeyer Kimberly A, Coler Rhea N
Infectious Disease Research Institute, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.
Eur J Immunol. 2016 Dec;46(12):2719-2729. doi: 10.1002/eji.201646399. Epub 2016 Nov 9.
The contribution of B cells to immunity against many infectious diseases is unquestionably important and well characterized. Here, we sought to determine the role of B cells in the induction of T-helper 1 (T 1) CD4 T cells upon vaccination with a tuberculosis (TB) antigen combined with a TLR4 agonist. We used B-cell deficient mice (μMT ), tetramer-positive CD4 T cells, markers of memory "precursor" effector cells (MPECs), and T-cell adoptive transfers and demonstrated that the early antigen-specific cytokine-producing T 1 responses are unaffected in the absence of B cells, however MPEC induction is strongly impaired resulting in a deficiency of the memory T 1 response in μMT mice. We further show that antigen-presentation by B cells is necessary for their role in MPEC generation using B-cell adoptive transfers from wt or MHC class II knock-out mice into μMT mice. Our study challenges the view that B-cell deficiency exclusively alters the T 1 response at memory time-points. Collectively, our results provide new insights on the multifaceted roles of B cells that will have a high impact on vaccine development against several pathogens including those requiring T 1 cell-mediated immunity.
B细胞对许多传染病免疫的贡献无疑是重要的，并且已有充分的研究。在此，我们试图确定在用结核（TB）抗原与TLR4激动剂联合接种疫苗时，B细胞在诱导辅助性T细胞1（Th1）CD4 T细胞中的作用。我们使用了B细胞缺陷小鼠（μMT）、四聚体阳性CD4 T细胞、记忆“前体”效应细胞（MPEC）标志物以及T细胞过继转移，结果表明在没有B细胞的情况下，早期抗原特异性产生细胞因子的Th1反应不受影响，然而MPEC的诱导受到严重损害，导致μMT小鼠中记忆性Th1反应不足。我们进一步表明，使用从野生型或MHC II类敲除小鼠向μMT小鼠进行B细胞过继转移，B细胞的抗原呈递对于其在MPEC产生中的作用是必要的。我们的研究挑战了B细胞缺陷仅在记忆时间点改变Th1反应的观点。总体而言，我们的结果为B细胞的多方面作用提供了新的见解，这将对针对几种病原体（包括那些需要Th1细胞介导免疫的病原体）的疫苗开发产生重大影响。
