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

Autor:	Ortiz Y; Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg 79104, Germany.; Faculty of Biology, Signalling Research Centers Centre for Integrative Biological Signalling Studies and Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany., Anasti K; Department of Medicine & Pathology, Human Vaccine Institute, Duke University, Durham, NC 27703., Kane AP; Department of Medicine & Pathology, Human Vaccine Institute, Duke University, Durham, NC 27703., Cronin K; Department of Medicine & Pathology, Human Vaccine Institute, Duke University, Durham, NC 27703., Alam SM; Department of Medicine & Pathology, Human Vaccine Institute, Duke University, Durham, NC 27703.; Deparment of Medicine and Pathology, Duke University, Durham NC 27703., Reth M; Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg 79104, Germany.; Faculty of Biology, Signalling Research Centers Centre for Integrative Biological Signalling Studies and Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 30; Vol. 121 (31), pp. e2404728121. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.1073/pnas.2404728121
Abstrakt:	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 CH1γ 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. Competing Interests: Competing interests statement:M.R. has co-authored several review articles with reviewer M.R.G. in the past 4 y.
Databáze:	MEDLINE
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