Impaired B Cell Response During COVID-19
Regulated and controlled B cell response is critical for the effective immune response against the CoVs, as discussed above. However, under certain conditions, B cell response may be detrimental and aggravate the underlying disease condition. A notion has emerged, which suggests that in COVID-19 patients, B cell number though reduced, but these cells display robust activation in some cases that correlate with disease severity.
Deep immune profiling integrated with computational approach revealed intricate relations of B cell response with clinical parameters at various stages of the COVID-19 disease severity. These cells express proliferation (Ki67+), differentiation (CD27+ CD38+), as well as exhaustion markers (PD-1+). More robust expression of these markers was observed in severe cases compared to mild-moderate, with an overall decrease in memory B cell number (Mathew et al., 2020). Further, 70% of the patients reported have IgG and IgM S protein-specific antibodies, suggesting activation status of the antibody-secreting plasmablasts. Thus, this study shows that B cells, in severe cases, display concomitant activation and exhaustion markers, while mild cases or healthy controls showed a normal response. However, how this activated status of B cells had an impact on disease severity was not studied. By looking at the alleged relationship of activated B cells with disease severity, Woodruff et al. (2020) showed robust activation status of extrafollicular B cells which resembled their behavior in autoimmune condition. The activation status of these cells was found more pronounced in critically ill patients (n = 10) than non-critical (n = 7) and healthy control (n = 17), which correlated with SARS-CoV-2-specific antibody production and disease progression. Further, an increase in antibody-secreting cells (ASCs) was found in critically ill cases compared to non-severe cases along with an increase in S protein-specific antibodies, probably with a non-neutralizing property. This study shows that in some patients with a critical disease condition, robust B cell response and presence of SARS-CoV-2 antigen-specific antibodies may be associated with worsening of the disease condition. The ASCs were identified as the population of cells with CD138+ and CD21low expression. However, no comparison was drawn between various age groups concerning disease severity. While across studies, B cell activation is apparent in severe cases, it is subsequently associated with a sharp decline in their number. Various mechanisms may be responsible for this decline, among which B cell exhaustion is one, but still poorly understood (Yi et al., 2010).
A recent study has provided mechanistic insights into how some cases of COVID-19 exhibit low B cell number. Kaneko et al. (2020) studied the post-mortem samples (n = 11) of thoracic lymph nodes and spleens and found that Bcl-6+ germinal center (GC) B cells highly reduced in these patients in comparison to non-COVID-19 control (n = 6). This decline in GC was also associated with a decrease in TFH cell differentiation and an increase in the number of TH1 cells (Kaneko et al., 2020). Further, an increase in expression of TNF-α levels was found in the follicles. Based on previous studies that TNF-α inhibits the lymphoid follicular development, and high levels of this pleiotropic cytokine is the hallmark of COVID-19, the authors attributed the reduction in GC to high levels of this cytokine. In addition to the study in post-mortem samples, the authors conducted B cell analysis in peripheral blood samples from COVID-19 patients at different stages of the disease. In line with the post-mortem data, patients with severe disease condition (n = 25) had a significant decrease in the number of naïve B cells, CD19+ B cells, and follicular B cell subsets in comparison to the healthy controls (n = 4), convalescent patients (n = 39), and moderate patients (n = 4). Thus, this study provides a probable cause for the B cell decline in severe cases of Covid-19. However, there was a significant difference in the mean age of severe patients (higher between 58 and 60) than the control, convalescent, and moderate group (30–45 years). Thus, the effect of age on the decline in B cells cannot be undermined in this study. More studies are needed to specifically look into the B cell number and activation status in COVID-19 patients concerning the disease severity to get a clear understanding of the role of these cells.