Ehrhardt R O, Harriman G R, Inman J K, Lycke N, Gray B, Strober W
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Eur J Immunol. 1996 Aug;26(8):1926-34. doi: 10.1002/eji.1830260838.
In the present studies, we compared the activation requirements of sIgM+/sIgD+ B cells with those of isotype-switched sIgM-/sIgA+ B cells. We found that whereas sIgM+ B cells respond to T cell-independent (TI) and T cell-dependent (TD) Ag with no significant bias toward one stimulus, sIgA+ B cells were deficient in their ability to respond to antigen receptor cross-linking but responded remarkably well to TD stimuli. Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dextran), anti-kappa-dextran, or various immobilized anti-IgA antibodies (Ab) induced only low-level IgA B cell proliferation and no IgA secretion in the presence of various lymphokines; in marked contrast, sIgA+ B cells responded to cognate and noncognate T cell stimulation as well as to stimulation by CD40 ligand-bearing fibroblasts by secreting large amounts of IgA (up to 240 000 ng/ml per 10(5) cells). This pattern of sIgA+ B cell responsiveness was noted with both germinal center peanut agglutininhi (PNAhi) and non-germinal center PNAlo B cells. In confirmation of these results, whole Peyer's patch or lamina propria cell populations containing less than 15% sIgA+ B cells stimulated with a noncognate T cell stimulus or T cell membranes secreted mainly IgA (68%-94% of the total Ig secreted) and relatively little IgM. The strict T cell dependence of IgA B cell activation and differentiation provides important insights into immune responses of mucosal tissues and must be considered in the development of vaccines, particularly those designed to stimulate mucosal tissues containing large numbers of isotype-switched B cells.
在本研究中，我们比较了sIgM+/sIgD+ B细胞与同种型转换的sIgM-/sIgA+ B细胞的激活需求。我们发现，sIgM+ B细胞对非T细胞依赖性（TI）和T细胞依赖性（TD）抗原均有反应，对一种刺激无明显偏向，而sIgA+ B细胞对抗抗原受体交联的能力不足，但对TD刺激反应良好。因此，在存在各种淋巴因子的情况下，葡聚糖偶联的抗IgA抗体（抗IgA-葡聚糖）、抗κ-葡聚糖或各种固定化抗IgA抗体（Ab）仅诱导低水平的IgA B细胞增殖，且无IgA分泌；与之形成鲜明对比的是，sIgA+ B细胞通过分泌大量IgA（每10(5)个细胞高达240 000 ng/ml）对同源和非同源T细胞刺激以及携带CD40配体的成纤维细胞的刺激作出反应。生发中心花生凝集素高（PNAhi）和非生发中心PNA低（PNAlo）B细胞均呈现这种sIgA+ B细胞反应模式。为证实这些结果，用非同源T细胞刺激或T细胞膜刺激含有少于15% sIgA+ B细胞的整个派尔集合淋巴结或固有层细胞群体，主要分泌IgA（占总分泌Ig的68%-94%），而IgM分泌相对较少。IgA B细胞激活和分化对T细胞的严格依赖性为黏膜组织的免疫反应提供了重要见解，在疫苗开发中必须予以考虑，尤其是那些旨在刺激含有大量同种型转换B细胞的黏膜组织的疫苗。
