The CH1 domain influences the expression and antigen sensing of the HIV- specific CH31 IgM- BCR and IgG- BCR

• 成果类型: Article
• 署名作者: Ortiz, Yaneth; Anasti, Kara; Kane, Advaiti Pai; Cronin, Kenneth; Alam, S. Munir; Reth, Michael
• 署名单位: University of Freiburg; University of Freiburg; University of Freiburg; Duke University; Duke University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-15139
• DOI: 10.1073/pnas.2404728121
• 发表日期: 2024-07-30
• 关键词: heavy-chain; antibody; germline; affinity; broad; coevolution; maturation; complexes; infection; cells

摘要

How different classes of the B cell antigen receptor (BCR) sense viral antigens used in vaccination protocols is poorly understood. Here, we study antigen binding and sensing of human Ramos B cells expressing a BCR of either the IgM or IgG1 class with specificity for the CD4- binding- site of the envelope (Env) protein of the HIV- 1. Both BCRs carry an identical antigen binding site derived from the broad neutralizing antibody (bnAb) CH31. We find a five times higher expression of the IgG1-BCR in comparison to the IgM-BCR on the surface of transfected Ramos B cells. The two BCR classes also differ from each other in their interaction with cognate HIV Env antigens in that the IgG1-BCR and IgM-BCR bind preferentially to polyvalent and monovalent antigens, respectively. By generating an IgM/IgG1 chimeric BCR, we found that the class- specific BCR expression and antigen- sensing behavior can be transferred with the CH1 gamma domain from the IgG1-BCR to the IgM-BCR. Thus, the class of CH1 domain has an impact on BCR assembly and expression as well as on antigen sensing.