Isotype switching in human memory B cells sets intrinsic antigen- affinity thresholds that dictate antigen- driven fates

• 成果类型: Article
• 署名作者: Ambegaonkar, Abhijit A.; Holla, Prasida; Sohn, Haewon; George, Rachel; Tran, Tuan M.; Pierce, Susan K.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Indiana University System; Indiana University Bloomington; Regeneron; Indiana University System; Indiana University Bloomington
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9560
• DOI: 10.1073/pnas.2313672121
• 发表日期: 2024-03-19
• 关键词: germinal center b; lived plasma-cells; responses; antibodies; activation; reveal

摘要

Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GC) B cells. The human MBC compartment contains both switched IgG+ and unswitched IgM+ MBCs; however, whether these MBC subpopulations are equivalent in their response to B cell receptor cross- linking and their resulting fates is incompletely understood. Here, we show that IgG+ and IgM+ MBCs can be distinguished based on their response to x - specific monoclonal antibodies of differing affinities. IgG+ MBCs responded only to high - affinity anti -x and differentiated almost exclusively toward PC fates. In contrast, IgM+ MBCs were eliminated by apoptosis by high - affinity anti -x but responded to low - affinity anti -x by differentiating toward GC B cell fates. These results suggest that IgG+ and IgM+ MBCs may play distinct yet complementary roles in response to pathogen challenge ensuring the immediate production of high- affinity antibodies to homologous and closely related challenges and the generation of variant - specific MBCs through GC reactions.