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Proc Natl Acad Sci U S A ; 121(31): e2404728121, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39042672

ABSTRACT

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.


Subject(s)
HIV-1 , Immunoglobulin G , Immunoglobulin M , Receptors, Antigen, B-Cell , Humans , Immunoglobulin M/immunology , Immunoglobulin G/immunology , Receptors, Antigen, B-Cell/metabolism , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/immunology , HIV-1/immunology , HIV-1/genetics , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , HIV Antibodies/immunology , Protein Domains , Antibodies, Neutralizing/immunology
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