An efficient immunoassay for the B cell help function of SARS-CoV-2-specific memory CD4+ T cells.

The B cell "help" function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B cocultures for quantitative measurement of T cell-dependent B cell responses, with as few as ∼90 T cells. Utilizing M. tuberculosis (Mtb), we show that early priming and activation of CD4+ T cells is important for productive interaction between T and B cells and that similar effects are achieved by supplementing cocultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and stem cell growth factor (SCGF)/C-type lectin domain family 11 member A (CLEC11A), but this alone does not fully recapitulate the effects of monocyte supplementation. Importantly, we demonstrate improved activation and immunological output of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory CD4+ T-B cell cocultures with the inclusion of monocytes. This method may therefore provide a more sensitive assay to evaluate the B cell help quality of memory CD4+ T cells, for example, after vaccination or natural infection.