Trend Stephanie, Leffler Jonatan, Teige Ingrid, Frendéus Björn, Kermode Allan G, French Martyn A, Hart Prue H
Inflammation Laboratory, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA, Australia.
Front Immunol. 2021 Jan 11;11:614492. doi: 10.3389/fimmu.2020.614492. eCollection 2020.
B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM B cell subsets, including naive and IgM MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed. The reduction of TNF but not IL-10 expression in controls mediated by IgG immune complexes was reversed by CD32b blockade in naive and IgM MZ-like B cells only. However, no consequence of lower CD32b expression on these cells from females with CIS or MS was detected. Our findings highlight a potential role for naive and marginal zone-like B cells in the immunopathogenesis of MS in females, which requires further investigation.
B细胞对多发性硬化症（MS）的发展至关重要，但其导致该疾病的机制尚不清楚。我们推测，CD32b（FcγRIIb）在B细胞中具有抑制活性，是IgG Fc区域的受体，在临床孤立综合征（CIS）或MS患者的B细胞亚群上表达较低。在健康对照中，CD32b表达在幼稚后IgM B细胞亚群上最高。与对照女性相比，MS或CIS女性的IgM B细胞亚群（包括幼稚和IgM MZ样B细胞）上的CD32b表达显著降低。这些B细胞亚群上较低的CD32b表达与可检测到的抗爱泼斯坦-巴尔病毒衣壳抗原IgM抗体以及较高的血清B细胞活化因子水平相关。为了研究较低CD32b表达的影响，在有或没有CD32b阻断抗体的情况下，在IgG免疫复合物存在下对B细胞进行多克隆激活，并评估B细胞亚群中TNF和IL-10的表达。仅在幼稚和IgM MZ样B细胞中，CD32b阻断可逆转IgG免疫复合物介导的对照中TNF表达的降低，但不影响IL-10表达。然而，未检测到CIS或MS女性这些细胞上较低CD32b表达的后果。我们的研究结果突出了幼稚和边缘区样B细胞在女性MS免疫发病机制中的潜在作用，这需要进一步研究。
