In COVID-19, antigen size lower or larger than 70 kDa modulates the sepsis and memory B cells

Abstract

This review pretends to shed light on the immune processes occurring in the coronavirus disease 2019 (COVID-19) from a perspective based on the antigens size, lower or larger than 70 kDa. This cutoff size point explains the host type of immune response against the antigenic proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to the development of the memory B cells or, conversely, the immune suppression, apoptosis, viral escape, and sepsis. Here, based on previous experimental work and the review of related literature, the following is proposed: antigens < 70 kDa can access the germinal center through the follicular conduits, where the activated B cells can present the processed antigen to specific naive CD4+ T cells that, in interaction with the major histocompatibility complex class II (MHC-II), trigger the immune response T helper type 2 (Th2). Conversely, antigens > 70 kDa cannot circulate through the narrow follicular conduits network and might be captured within the subcapsular sinus by the macrophages and dendritic follicular cells. Then, these cognate antigens are presented, via complement receptors, to the B cells that acquire and present them through the MHC-II to the specific naive CD4+ T cells, triggering the immune response Th1. The sustained infected cells lysis can overfeed high levels of unassembled viral proteins < 70 kDa, which can lead to a strong and persistent B cell receptor (BCR) activation, enhancing the Th2 immune response, releasing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) that may lead to the immune paralysis, apoptosis, sepsis, and death. Finally, it is suggested that the polymerization of the viral antigens < 70 kDa into an antigenic polymer > 70 kDa could shift the immune response type from Th2 to Th1, developing the memory B cells and immunoglobulin G2 (IgG2) production, and avoiding the sepsis.