B lymphocytes (B cells) are the antibody producing cells of our body. They respond to specific antigens as well as non specific microbial patterns. The integration of these multiple signals determine if and how they will get activated.
Upon initial activation, while some cells proliferate and differentiate into more professional antibody secreting cells, some got eliminated. Understanding the factors that determine these fate decisions are of key importance in developing new and effective vaccines that generate long lasting protective antibody responses. Furthermore, the problems in regulation of these processes are often reasons why our body can not get rid of certain infections or why our body reacts to self molecules and leads to a set of autoimmune disorders.
Recently, our group showed that activation of B cells by antigens, while priming the cells metabolically for further differentiation, is not sufficient to lead the entire process. As a check point controller, cells need to receive a second stimulation either in the form of microbial signals that would confirm the existence of a real infection, or from helper T cells (the master regulators of the immune response) that would confirm that this is not a reaction against self molecules within 9 hours.
Only after the second ‘go’ signal, B cells continue to differentiate and generate a global immune response. If the second stimulation is not received in this time window, the antigen mediated initial stimulation initiated dead clock kills the cell by causing mitochondrial dysfunction. This novel mechanism explains how check points in the immune system operate for B cells in order to prevent autoimmunity or unnecessary immune activation. This work is published recently in Nature Immunology Second signals rescue B cells from activation-induced mitochondrial dysfunction and death.
This finding also shows that for survival and differentiation, microbial signals through Toll like receptors are as efficient as the signals coming from T cells and therefore, negate the need for B cells to engage in B cell-T cell interaction which would lead to high affinity protective antibodies. Therefore it explains why microbial ligands despite their superiority in inducing immune response are not often good candidates as vaccine adjuvants which we explained earlier this year in a research article published in the same journal Toll-like receptor 9 antagonizes antibody affinity maturation.
Altogether, these work will surely open new avenues of research that would increase our understanding of the key dynamics of the immune system.