Peddaboina Chander, Iannucci Jaclyn, Tobin Richard P, Shapiro Lee A, Newell Rogers M Karen
Department of Medical Physiology, Texas A&M University College of Medicine, Bryan, TX 77807, USA.
Department of Neuroscience and Experimental Therapeutics, Texas A&M University College of Medicine, Bryan, TX 77807, USA.
Int J Mol Sci. 2025 Jun 24;26(13):6054. doi: 10.3390/ijms26136054.
B cells contribute to innate and adaptive immunity. In the former, Toll-like receptor (TLR) activation promotes the expansion of inflammatory B cells. In the latter, B cell receptor (BCR) activation results in the production of antibodies or autoantibodies. Antigen processing and presentation are closely associated with major histocompatibility class II (MHC-II) and its companion protein, class II invariant peptide (CLIP). The impact of autophagy on the regulation of these unique mechanisms of B cell activation and subset expansion has not been fully explored. The results from the current study show that activating autophagy with rapamycin (RAPA) or inhibiting autophagy with hydroxycholoroquine (HCQ) differentially influences the TLR9 and BCR activation of B cells. These differences include the selective expansion of B1 and B2 B cell subsets, the regulation of the cell-surface expression of MHC-II and CLIP, and the ability of distinct B cell subsets to present peptide antigens. These novel findings demonstrate that the unique B cell activation mechanisms induced by TLR9 and BCR activation are differentially influenced by RAPA and HCQ, owing to the selective modulation of B cell subset expansion, and antigen processing and presentation by MHC-II proteins.
B细胞对固有免疫和适应性免疫均有贡献。在固有免疫中，Toll样受体（TLR）激活可促进炎性B细胞的扩增。在适应性免疫中，B细胞受体（BCR）激活会导致抗体或自身抗体的产生。抗原加工和呈递与主要组织相容性复合体II类（MHC-II）及其伴侣蛋白II类恒定肽（CLIP）密切相关。自噬对B细胞激活和亚群扩增这些独特机制的调节作用尚未得到充分研究。当前研究结果表明，用雷帕霉素（RAPA）激活自噬或用羟氯喹（HCQ）抑制自噬会对B细胞的TLR9和BCR激活产生不同影响。这些差异包括B1和B2 B细胞亚群的选择性扩增、MHC-II和CLIP细胞表面表达的调节，以及不同B细胞亚群呈递肽抗原的能力。这些新发现表明，由于B细胞亚群扩增以及MHC-II蛋白对抗原加工和呈递的选择性调节，TLR9和BCR激活诱导的独特B细胞激活机制受到RAPA和HCQ的不同影响。
