Merchant M S, Garvy B A, Riley R L
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA.
Blood. 1996 Apr 15;87(8):3289-96.
Surface IgM+B220+ B cell precursors can be categorized as either leukosialin (CD43/S7) negative (late stage pre-B cells) or positive (pro-B/early pre-B cells). In autoimmune New Zealand Black (NZB) mice, bone marrow small pre-B cells (IgM-CD43-B220+) and pro-B/early pre-B cells (IgM-CD43+B220+) declined significantly with age. In particular, subpopulations of pro-B/early pre-B cells expressing the heat stable antigen (HSA) were found in lower proportions with age. Significant decreases in interleukin-7 (IL-7) colony forming units (CFU) were also seen in NZB mice by 6 to 8 months of age and accompanied alterations in the numbers of pro-B and pre-B cells in bone marrow. Concomitant with reduced numbers of B lineage precursor cells and IL-7 CFU in vivo, NZB mice produced serum IgM antibodies that strongly inhibited IL-7 CFU responses in vitro. Two monoclonal IgM antibodies (5G9, 2F5) derived from LPS stimulated 10-month-old NZB splenocytes recognized pre-B cell surface antigens on both pre-B cell lines and on IL-7 stimulated bone marrow pro-B/pre-B cells. However, these monoclonal antibodies (MoAb) failed to significantly stain ex vivo bone marrow cells. The 5G9 and 2F5 MoAbs also partially inhibited IL-7 CFU in vitro. These results suggest that NZB bone marrow becomes increasingly deficient in B cell precursors and especially in IL-7 responsive pre-B cells with age. IgM serum antibodies and monoclonal IgM antibodies derived from older NZB mice inhibit pre-B cell growth to IL-7. The production of such autoantibodies may interfere with B cell development in aging NZB mice by preventing IL-7-mediated proliferation.
表面免疫球蛋白M（Surface IgM）+B220+B细胞前体可分为白细胞唾液酸蛋白（CD43/S7）阴性（晚期前B细胞）或阳性（前B/早期前B细胞）。在自身免疫性新西兰黑（NZB）小鼠中，骨髓小前B细胞（IgM-CD43-B220+）和前B/早期前B细胞（IgM-CD43+B220+）随年龄显著减少。特别是，表达热稳定抗原（HSA）的前B/早期前B细胞亚群随年龄比例降低。到6至8月龄时，NZB小鼠的白细胞介素-7（IL-7）集落形成单位（CFU）也显著减少，并伴有骨髓中前B细胞和前B细胞数量的改变。与体内B系前体细胞和IL-7 CFU数量减少同时，NZB小鼠产生的血清IgM抗体在体外强烈抑制IL-7 CFU反应。源自脂多糖刺激的10月龄NZB脾细胞的两种单克隆IgM抗体（5G9、2F5）识别前B细胞系以及IL-7刺激的骨髓前B/前B细胞上的前B细胞表面抗原。然而，这些单克隆抗体（MoAb）未能显著标记体外骨髓细胞。5G9和2F5 MoAb在体外也部分抑制IL-7 CFU。这些结果表明，随着年龄增长，NZB骨髓中B细胞前体越来越缺乏，尤其是对IL-7有反应的前B细胞。来自老年NZB小鼠的IgM血清抗体和单克隆IgM抗体抑制前B细胞对IL-7的生长。此类自身抗体的产生可能通过阻止IL-7介导的增殖而干扰衰老NZB小鼠的B细胞发育。
