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CD11c, FcRL5, or T‐bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remains largely unclear. We have assessed the co‐expression of CD11c, T‐bet, and FcRL5 in an in vitro B‐cell culture system to determine how stimulation via the BCR, toll‐like receptor 9 (TLR9), and different cytokines influence CD11c, T‐bet, and FcRL5 expression. We observed different expression dynamics for all markers, but a largely overlapping regulation of CD11c and FcRL5 in response to BCR and TLR9 activation, while T‐bet was strongly dependent on IFN‐γ signaling. Investigating plasma cell differentiation and APC functions, there was no association between marker expression and antibody secretion or T‐cell help. Rather the functions were associated with TLR9‐signalling and B‐cell‐derived IL‐6 production, respectively. These results suggest that the expression of CD11c, FcRL5, and T‐bet and plasma cell differentiation and improved APC functions occur in parallel and are regulated by similar activation signals, but they are not interdependent. [ABSTRACT FROM AUTHOR]

The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-[gamma] production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3[zeta] chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response., Introduction The pathogenesis of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive. SARS-CoV-2 infection ranges from asymptomatic disease to multiorgan failure and death [...]