Administrative Supplement Covid19: Molecular Regulation of B cells and T cells in Human SLE

The COVID19 pandemic illustrates the urgent need for understanding human B cell responses to emergentpathogens and its application to assessing herd immunity. Our laboratories have described the phenotypic,immunological and molecular features of different arms of human B cell responses and in particular, the originalcharacterization of the human extrafollicular effector B cell activation pathway and its contribution to differentmemory and plasma cells responses. On that basis, we we propose to interrogate the different arms of the B cellresponse to the SARS-CoV-2 virus; to identify the B cell compartments that participate in the early, ongoing andlate post-infection responses; and to determine their contribution to the establishment of herd immunity, at leastin part through the generation of protective B cell memory. The latter is an essential feature that could beuncoupled from the persistence of serum antibodies; and therefore, would go unrecognized unless formallytested. We postulate that the establishment of cellular B cell memory and the ability to evaluate its magnitudeand quality will be critical to track the risk of the population to short-term re-infection and seasonal exposure; todesign vaccines capable to trigger this protective feature; and to develop SARS-CoV-2 B cell-based diagnostictests. These goals will be accomplished using blood samples from SARS-CoV-2-infected and convalescentindividuals through the following specific aims: Aim 1. Characterization of SARS-CoV-2-specific B cellresponses through multidimensional B cell flow cytometry A precise adjudication of the cellular origin,magnitude, and persistence of the anti-SARS-CoV-2 B cell response will be accomplished by antigen-specificflow cytometry and validated by multiplex antigen assays and single cell analysis of the B cell populations. Aim2. Measurement of SARS-CoV-2-specific B cell memory and herd immunity. Phenotypic features andantigen-specific flow cytometry assays established in aim 1, will be applied to intermediate and late post-infectiontime points in order to understand: a) the cellular compartments in which SARS-CoV-2-specific B cell memoryresides; b) its quality, magnitude and distribution within the population; c) its provenance (whether from early oflate cellular precursors); and d) its concordance or conversely, uncoupling from serological responses and thegeneration of long-lived plasma cells (LLPC).