Community Series in SARS-CoV-2 Variants, B Lymphocytes, and Autoreactivity: Volume II

This Research Topic is the second volume of the “SARS-CoV-2 Variants, B Lymphocytes, and Autoreactivity” Community Series. Please see Volume I here

Recent research into the immune response of COVID-19 patients has revealed significant changes in circulating B cell populations. These changes include shifts in naïve B cells, transitional B cells, plasmablasts, plasma cells, class-switched and unswitched memory B cells, T-bet+ B cells, CD27-IgD- double-negative B cells, and "innate-like" B cells. Antibody analysis against SARS-CoV-2 shows diverse characteristics, such as elongated CDR3 sequences with hydrophobic amino acids, variations in mutation rates within heavy-chain variable regions, and the accumulation of somatic mutations in virus-specific memory B cells over time—a sign of antigen-driven B cell responses.

Post-mortem analyses of COVID-19 patients have identified issues in germinal center formation within the spleen and thoracic lymph nodes. This suggests that plasma cells may be generated through thymus-independent B cell activation, resulting in fewer somatic mutations. However, there is evidence of somatic mutation accumulation in SARS-CoV-2-specific B cells, which typically indicates germinal center-dependent responses, contrasting with the early extrafollicular immune response seen in SARS-CoV-2 infection.

COVID-19 is also linked to auto-inflammatory disorders, such as autoimmune cytopenia, Guillain-Barre syndrome, Kawasaki disease, and anti-phospholipid syndrome. Some anti-SARS-CoV-2 antibodies cross-react with tissues in the brain, lungs, heart, kidneys, and gut. Disturbingly, certain patients with severe pneumonia have autoantibodies against interferon and related cytokines. Although the mechanism of tissue damage is not fully understood, self-reactive antibodies may contribute to some clinical symptoms.

As SARS-CoV-2 continues to mutate, new viral variants may evade memory B cells and increase transmission or severity. Mild COVID-19 cases may face re-infection risks, emphasizing the need for updated vaccines. Understanding these escape mutations' effects on B cells is crucial for developing new vaccines that incorporate these changes.

This Research Topic aims to explore these themes by examining:

- The B cell repertoire throughout infection stages
- The role of somatic and junctional mechanisms in B cell formation
- Tissue-resident B cell distribution, particularly in the lungs
- Mechanisms of germinal center-dependent and extrafollicular responses
- Factors affecting affinity-maturation and memory B cell formation
- The origin and stability of the humoral response to variants
- Long-term memory B cell duration in infected and vaccinated individuals
- The influence of cross-reactive B cells on immune memory
- The relationship between respiratory parameters and memory B cell changes
- Autoreactive B cells’ emergence and pathogenic roles
- Outcomes of autoreactive B cell responses post-infection
- Potential protective roles of autoreactive antibodies
- Contributions of B cell tolerance mechanisms to disease progression

This Research Topic seeks to foster discussions and insights into adaptable immune tolerance mechanisms across different demographics and predispositions.