FIGURE 2.

Lymphoid and circulating T_FH responses in COVID‐19. SARS‐CoV‐2 antigen in the lymph nodes results in activation of antigen‐specific B cells and T_FH cells. Their interaction leads to the initiation of the germinal center reaction. This results in the development of memory B cells with increased somatic hypermutation (SHM) and increased affinity, as well as long‐lived plasma cells that traffic to the bone marrow and provide a long‐term source of neutralizing antibodies. A population of short‐lived antibody‐secreting cells (ASCs) appears in the circulation and provides a raid source of neutralizing antibodies. Concurrently, a population of activated (CD38⁺, PD‐1⁺, ICOS⁺) cT_FH cells appears in the circulation. This population contains antigen‐specific cT_FH cells (not depicted). Although memory B cells and ASCs are primarily located in lymphoid tissues, they are typically measured in blood samples, where they correlate with activated cT_FH cells. Activated cT_FH cells also correlate with the development of neutralizing antibodies. These cT_FH cells are a potential biomarker of T_FH activity in lymphoid tissues but it remains to be determined if this population of cT_FH cells are predictive of long‐term neutralizing antibodies, or of the development of long‐lived plasma cells and the prolonged evolution of the MBC pool. The figure was created with BioRender.com