Figure 10. Lymph node germinal centers—key to memory B-cell development—are disrupted by COVID-19.

A. Naïve CD4⁺ T-cells are activated in the T-cell zone by antigen-presenting dendritic cells (DC).¹⁴¹ This includes the generation of follicular helper T lymphocytes (T_FH), which upregulate CXC-chemokine receptor 5 (CXCR5) expression before activating B-cells at the T-B border. Both cell types migrate to B-cell-follicles to form germinal centers.¹⁴¹ Active cooperation of T_FH with germinal center B-cells promotes immunoglobulin hypermutation, class switching and affinity maturation, during which B-cells differentiate into memory cells and long-lived plasma cells. (FDC: Follicle dendritic cell; BCR: B-cell receptor; MHC: major histocompatibility complex; TCR: T-cell receptor). Reprinted with permission from ref 141 under a Creative Commons Attribution-Noncommercial (CC BY-NC 4.0) License. Copyright 2014 The Authors. B. Acutely ill COVID-19 patients carrying high viral loads exhibit a striking absence of germinal centers, with a marked reduction of germinal center B-cells and T_FH cells.^27,210 Although there is robust activation of nongerminal center B-cells, this does not give rise to long-lived memory B-cells or the production of high affinity antibodies. Reprinted with permission from ref 27. Copyright 2020 Elsevier.