The Graduate Group in Immunology, University of California, Davis, Davis, CA 95616, USA.
Eur J Immunol. 2012 Jan;42(1):120-9. doi: 10.1002/eji.201141890. Epub 2011 Nov 28.
Natural IgM antibodies secreted in the absence of antigenic challenge are important contributors to antimicrobial immunity and tissue homeostasis. Early studies identified BM and, to a lesser extent the spleen, as main tissue sources of this spontaneously secreted IgM. However, the responsible B-cell subset has never been identified. Using multicolor flow cytometry, cell sorting and chimeric mice in which B-1 and B-2 cells and their secreted antibodies are distinguished by their Ig-allotype, we unequivocally identify the natural IgM-secreting cells in spleen and, for the first time, in the BM as IgM(+) IgD(lo/-) CD19(hi) CD43(+) CD5(+/-) B-1 cells. The newly identified population of BM B-1 cells shows many of the phenotypic characteristics of splenic B-1 cells but is distinct from B-1 cells in the peritoneal cavity, which generate at best very small amounts of IgM. Antibody-secreting spleen and BM B-1 cells are distinct also from terminally differentiated plasma cells generated from antigen-induced conventional B cells, as they express high levels of surface IgM and CD19 and lack expression of CD138. Overall, these data identify populations of non-terminally differentiated B-1 cells in spleen and BM as the most significant producers of natural IgM.
天然 IgM 抗体在没有抗原刺激的情况下分泌，是抗菌免疫和组织稳态的重要贡献者。早期的研究确定了骨髓（BM），以及在较小程度上的脾脏，是这种自发分泌的 IgM 的主要组织来源。然而，负责产生这种抗体的 B 细胞亚群从未被鉴定过。使用多色流式细胞术、细胞分选和嵌合小鼠，我们可以通过其 Ig 同种型区分 B-1 和 B-2 细胞及其分泌的抗体，明确地鉴定出脾脏和 BM 中天然 IgM 分泌细胞，这是首次在 BM 中鉴定出 IgM(+)IgD(lo/-)CD19(hi)CD43(+)CD5(+/-)B-1 细胞。新鉴定的 BM B-1 细胞群表现出许多与脾脏 B-1 细胞相似的表型特征，但与腹腔中的 B-1 细胞不同，后者只能产生少量的 IgM。分泌抗体的脾脏和 BM B-1 细胞也与抗原诱导的常规 B 细胞产生的终末分化浆细胞不同，因为它们表达高水平的表面 IgM 和 CD19，并且缺乏 CD138 的表达。总的来说，这些数据表明，脾脏和 BM 中未终末分化的 B-1 细胞群是天然 IgM 的最重要产生者。
