Week 1, May 2024: B Cells Producing Antibodies

B cells, or B lymphocytes, are a crucial component of the adaptive immune system and humoral immunity. They originate from the bone marrow and mature in secondary lymphoid organs, such as the spleen and lymph nodes. The B cell receptor (BCR) is generated through genetic rearrangement to recognize specific antigens. Upon encountering the antigen, typically on the surface of pathogens or presented by antigen-presenting cells, B cells proliferate and differentiate into plasma cells or memory B cells. Plasma cells are responsible for the production and secretion of antibodies.

Recent research has focused on improving affinity maturation to help B cells produce antibodies that are more protective. For instance, researchers from Boston Children's Hospital published a study in Nature Portfolio describing the in vivo affinity maturation of mouse B cells reprogrammed to express human antibodies. Using CRISPR, they edited mouse B to express human antibody light and heavy chains with the goal of evaluating candidate vaccines and develop better antibody therapies. They also used this approach to increase potency of anti-SARS-CoV-2 antibodies against Omicron strains.

However, the antibodies produced by B cells may not be attacking foreign pathogens but can also end up attacking the body’s own tissues. A study by Akama-Garren et al. found that follicular T cells give signals to help B cells, and this is essential in adaptive immunity, driving tolerogenic B cell responses. The researchers describe how some particular follicular T cells may instead cause the formation of B cells which produce auto-reactive antibodies. These results could assist in developing treatments for autoimmune diseases like lupus and rheumatoid arthritis.

Meanwhile, in the field of autoimmune conditions and organ transplants, researchers from Nippon Medical School studied how disulfiram treatment (which is typically used to treat alcohol dependence) suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism. In a previous study, they found that inhibiting the cytoplasmic protein FROUNT with disulfiram suppresses macrophage activation and migration, thus treating inflammatory diseases. Now, the team showed the effectiveness of DSF in antibody-producing reactions by directly inhibiting B cell responses, resulting in prolonged survival of a mouse model’s heart graft.