ABSTRACT
The B cell “help” function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B co-cultures for quantitative measurement of T cell-dependent B cell responses, with as few as ∼90 T cells. Utilizing 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 co-cultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and SCGF/CLEC11A, but this alone does not fully recapitulate the effects of monocyte-supplementation. Importantly, we demonstrate improved activation and immunological output of SARS-CoV-2 specific memory CD4+ T - B cell co-cultures 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. Graphical Ansari et al. describe an efficient T-B cell co-culture assay to assess B-cell help function of antigen-specific T helper cells in healthy and COVID-19 recovered individuals, based on the inclusion of monocytes. Increased B cell output in this assay may provide extra sensitivity to evaluate immunological responses in different contexts.