Wang Z, Chen Z J, Wheeler J, Shen S, Notkins A L
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda 20892-4322, USA.
Eur J Immunol. 2001 Apr;31(4):1106-14. doi: 10.1002/1521-4141(200104)31:4<1106::aid-immu1106>3.0.co;2-5.
Monoclonal polyreactive antibodies (Ab) can bind, at low affinity, a variety of different self and non-self antigens (Ag). Recent studies in humans showed that polyreactive Ab are expressed on the surface of a subset of peripheral B lymphocytes and clonal analysis revealed that a variety of different Ag can bind to single cells expressing these Ab. To see if these polyreactive Ag-binding B (PAB) cells also are present in mice, fluorescein-conjugated Ag and FACS sorting were used to identify and separate PAB cells from non-polyreactive Ag-binding B cells. Depending on the Ag used for screening, up to one-third of mouse splenic B cells displayed polyreactive Ag-binding properties. Confirmation that the Ag actually bound to surface Ig came from treating PAB cells with anti-Ig which inhibited Ag binding by up to 80 %. Further studies showed that PAB cells could present Ag to Ag-specific T cells, but despite their Ag-presenting ability, PAB cells from normal mice failed to trigger Ag-specific T cells to proliferate. Analysis of the co-stimulatory molecules B7-1 and B7-2 showed that these molecules were not expressed on PAB cells from normal mice. These findings argue that the lack of co-stimulatory molecules on PAB cells is the most likely explanation for their failure to stimulate Ag-specific T cells. The ability of PAB cells from normal mice to bind and present Ag to Ag-specific T cells, without causing them to proliferate, suggests that PAB cells may contribute to the induction and / or maintenance of immunological tolerance.
单克隆多反应性抗体（Ab）能够以低亲和力结合多种不同的自身和非自身抗原（Ag）。最近在人类中的研究表明，多反应性Ab在外周B淋巴细胞亚群的表面表达，克隆分析显示多种不同的Ag能够结合表达这些Ab的单个细胞。为了探究这些多反应性Ag结合B（PAB）细胞在小鼠中是否也存在，使用荧光素偶联的Ag和荧光激活细胞分选术（FACS）从非多反应性Ag结合B细胞中鉴定并分离出PAB细胞。根据用于筛选的Ag不同，高达三分之一的小鼠脾B细胞表现出多反应性Ag结合特性。通过用抗Ig处理PAB细胞，证实Ag实际上结合到了表面Ig上，这使Ag结合受到高达80%的抑制。进一步的研究表明，PAB细胞能够将Ag呈递给Ag特异性T细胞，但是尽管它们具有Ag呈递能力，正常小鼠的PAB细胞却未能触发Ag特异性T细胞增殖。对共刺激分子B7-1和B7-2的分析表明，这些分子在正常小鼠的PAB细胞上不表达。这些发现表明，PAB细胞上缺乏共刺激分子是其未能刺激Ag特异性T细胞的最可能原因。正常小鼠的PAB细胞能够结合Ag并将其呈递给Ag特异性T细胞，却不使其增殖，这表明PAB细胞可能有助于免疫耐受的诱导和/或维持。
