Fig 8. Diagrammatic representation illustrate the postulated role of naïve B cell in triggering humoral immune response in lung tissues of COVID-19 patients and the locations where B cell targeted therapeutic strategies function.

SARS-CoV-2 infection may activate and promote the adhesion and accumulation of naïve B cells to the mediastinal lymph node with β2 integrin (LFA-1) and α4β1 integrin. The increased infiltration of naïve B cells activated by spike proteins from SARS-CoV-2 secretes large amounts of IgM to promote extrafollicular response and humoral immune response. Monocytes are recruited and differentiate to macrophage in response to the robust humoral immune response. Secreted IgM simultaneously activates the complement system and Fc receptor in dendritic cells and macrophage to increase antigen presentation and phagocytosis to facilitate innate and adaptive immunity. On the other hand, high affinity or abundant SARS-CoV-2 presented by antigen-presenting cell (APC) such as dendritic cell may stimulate IL-12-dependent plasma cell differentiation in naïve B cells to produce more IgM, instead of promoting B cell proliferation and differentiation by CD40/CD40L signaling mediated germinal center formation. Ibrutinib inhibits B-cell growth by specifically inhibiting Bruton kinase, which is thought to be critical for the BCR signaling pathway; Natalizumab reduces B-cell migration by blocking α4β1 integrin. Fingolimod reduces B-cell egress out of the lymph node by stimulating S1PR1/3 to internalize the receptors.