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bioRxiv · 10.1101/2023.12.13.571545

Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain

Ortiz, Y.·Anasti, K.·Pane, A. K.·Cronin, K.·Alam, S. M.·Reth, M.
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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 Ramos B cells expressing BCRs of either the IgM or IgG1 class with a specificity for the CD4-binding-site of the envelope (Env) protein of the human immune deficiency virus-1 (HIV-1). We find that, in spite of their identical antigen binding site, the two BCR classes differ drastically from each other in that the IgM-BCR and IgG1-BCR bind preferentially to monovalent and polyvalent antigens, respectively. By generating an IgM/IgG1 chimeric BCR we found that the class-specific antigen-sensing behavior can be transferred with the CH1{gamma} domain from the IgG1-BCR to the IgM-BCR. Our results indicate that the class-switching process not only results in the production of antibody classes with different effector functions but also alters the antigen sensing of secondary B lymphocytes. These findings suggest that antigen valency in existing vaccination protocols should be modified and altered between primary versus secondary (booster) immunization.

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Ortiz, Y., Anasti, K., Pane, A. K., Cronin, K., Alam, S. M., Reth, M.. 2023-12-14. Class-specific sensing of HIV-1 antigens by the B cell antigen receptor depends on the CH1 domain. https://doi.org/10.1101/2023.12.13.571545

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