Thorarinsdottir K, Camponeschi A, Cavallini N, Grimsholm O, Jacobsson L, Gjertsson I, Mårtensson I-L
Department of Rheumatology and Inflammation Research, University of Gothenburg.
Rheumatology Clinic, the Sahlgrenska University Hospital, Gothenburg, Sweden.
Clin Exp Immunol. 2016 Aug;185(2):252-62. doi: 10.1111/cei.12795. Epub 2016 May 13.
The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co-receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation. Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21(-/low) ) are increased in conditions with chronic inflammation, e.g. autoimmune diseases. However, little is known about the CD21(-/low) B cell subset in peripheral blood from healthy donors. Here, we show that CD21(-/low) cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21(-/low) subset can be divided into CD38(-) 24(+) and CD38(-) 24(low) cells, where most of the CD38(-) 24(+) are CD27(+) immunoglobulin (Ig)M(+) IgD(+) and the CD38(-) 24(low) are switched CD27(-) . Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. In contrast to naive cells, the majority of CD21(-/low) cells lack expression of the ABCB1 transporter. Stimulation with a combination of BCR, Toll-like receptor (TLR)-7/8 and interleukin (IL)-2 induces proliferation and differentiation of the CD21(-/low) B cells comparable to CD21(+) CD27(+) memory B cells. The response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naive B cells. This is ascribed to a weaker response by the CD38(-) 24(low) subset, implying that some memory B cells require not only TLR but also BCR triggering. We conclude that the CD21(-/low) cells in healthy donors are memory B cells.
补体受体2（CR2，CD21）是作为B细胞受体（BCR）共受体的复合物（CD21/CD19/CD81）的一部分。同时触发BCR和CD21可降低B细胞活化的阈值。尽管CD21很重要，但在慢性炎症状态（如自身免疫性疾病）下，表达少量或缺乏表面CD21（CD21(-/low)）的B细胞会增多。然而，关于健康供体外周血中CD21(-/low) B细胞亚群的情况知之甚少。在此，我们表明，排除过渡性B细胞后，CD21(-/low)细胞约占成人外周血B细胞的5%，但在脐血中几乎检测不到。CD21(-/low)亚群可分为CD38(-) 24(+)和CD38(-) 24(low)细胞，其中大多数CD38(-) 24(+)是CD27(+)免疫球蛋白（Ig）M(+) IgD(+)，而CD38(-) 24(low)是类别转换的CD27(-)。其他标志物（如CD95和CD62L）的表达水平与经典记忆B细胞上的相似。与幼稚细胞不同，大多数CD21(-/low)细胞缺乏ABCB1转运蛋白的表达。用BCR、Toll样受体（TLR）-7/8和白细胞介素（IL）-2联合刺激可诱导CD21(-/low) B细胞增殖和分化，其程度与CD21(+) CD27(+)记忆B细胞相当。排除BCR激动剂后的反应不如经典记忆B细胞，但明显高于幼稚B细胞。这归因于CD38(-) 24(low)亚群的反应较弱，这意味着一些记忆B细胞不仅需要TLR触发，还需要BCR触发。我们得出结论，健康供体中的CD21(-/low)细胞是记忆B细胞。
