Control systems and decision making for antibody production

This paper synthesizes recent progress toward understanding the integrated control systems and fail-safes that guide the quality and quantity of antibody produced by B cells. We focus on four key decisions: (1) the choice between proliferation or death in perifollicular B cells in the first 3 days after antigen encounter; (2) differentiation of proliferating perifollicular B cells into extrafollicular plasma cells or germinal center B cells; (3) positive selection of B cell antigen receptor (BCR) affinity for foreign antigen versus negative selection of BCR affinity for self antigen in germinal center B cells; and (4) survival versus death of antibody-secreting plasma cells. Understanding the engineering of these control systems represents a challenging future step for treating disorders of antibody production in autoimmunity, allergy and immunodeficiency.