CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent
CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent
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DOI：
10.1111/imm.12800
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发表时间：
2017-12-01
期刊：
影响因子：
6.4
通讯作者：
George, Anna
中科院分区：
文献类型：
--
作者：
D'Souza, Lucas;Gupta, Sneh Lata;George, Anna
长期以来，b细胞记忆被认为是同型转换、体细胞突变和生发中心（GC）衍生的。然而，现在很清楚，内存池是一个复杂的混合物，包括未转换和未突变的细胞。此外，CD73、CD80和CD273的表达允许b细胞记忆分为多个亚群，随着GC的进展、同型转换和体细胞突变的获得，这些标记物的组合表达增加。我们已经扩展了这些发现，以确定这些标记是否可以用于识别IgM记忆表型是由t依赖性还是t非依赖性反应引起的。我们报告说，CD73表达鉴定了抗原经历的IgM（+）细胞的一个子集，这些细胞具有功能性b细胞记忆的属性。该亚群在t细胞缺陷和CD40缺陷小鼠的脾脏中减少，在用突变型和野生型骨髓制成的混合骨髓嵌合体中，CD73(+) IgM记忆的比例在t细胞缺陷的供体室中恢复，而在CD40缺陷的供体室中则没有，这表明CD40连接参与了其产生。我们还报道，CD40信号支持CD73在脾T细胞和年龄相关B细胞（abc）上的最佳表达，但不支持其他免疫细胞，如中性粒细胞、边缘区B细胞、腹腔B-1 B细胞和调节性T细胞和B细胞。我们的数据表明，除了在b细胞分化过程中促进gc相关记忆的产生外，cd40信号传导还可以影响未开关记忆b细胞池的组成。他们还提出了一小部分abc可能代表t细胞依赖性IgM记忆的可能性。
B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM(+) cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73(+) IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory.