Dr. Abhijit A. Ambegaonkar, National Institute of Allergy and Infectious Diseases (NIAID/NIH), Rockville, USA
Antibody immunological memory is the ability of the immune system to remember previous infections by disease-causing pathogens and upon reinfection with the same pathogen rapidly mount a protective antibody response of greater magnitude and higher affinity. Antibody memory is dependent on the acquisition of long-lived memory B cells (MBCs) following the initial infection. However, many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with a large expansion of a phenotypically and transcriptionally distinct subpopulation of B cells termed atypical MBCs. Atypical MBCs are distinguished by their high expression of a variety of inhibitory receptors and by their inability to respond to antigens in solution suggesting that atypical MBCs contribute to the poor acquisition of immunity in chronic infections. Clearly, the development of vaccines for chronic infectious diseases would benefit from a better understanding of the function of atypical MBCs. In my talk, I will discuss my work focused on two key features of atypical MBCs, first the conditions under which they are activated and second their affinity thresholds for antigen. Briefly, I demonstrated that atypical MBCs robustly respond to antigens associated with cell surfaces due in part to the ability of atypical MBCs to segregate the potent inhibitory receptor FcγRIIB from the B cell receptor (BCR) immune synapse. I speculate that during chronic infections atypical MBC expand to allow responses to foreign antigens that associate with cell surfaces, such as antigens in immune complexes, and to limit responses to fully soluble antigens, such as self-antigens. I also determined that a subpopulation of atypical MBCs that express high levels of IgD BCRs but low levels of IgM BCRs acquired high affinity thresholds for antigen-driven activation. I believe that this feature of atypical MBCs may also limit response to low affinity self antigens. These studies extend our understanding of the function of B cell subpopulations in chronic infectious diseases and provide critical insights for the design of vaccination strategies that can efficiently generate broadly neutralizing antibodies against infectious pathogens.
Meeting ID: 942 6405 2665