Division of labor during primary humoral immunity

Abstract

B lymphocytes are often considered a homogenous population. However, B cells in both mouse and humans are comprised of distinct subpopulations that differ in development, phenotype, function, and microenvironmental niches. Much of our understanding about how these different B-cells populations mount antibody responses has been derived from experimental findings in mouse models and based on the use of model antigens. These reductionist studies performed over decades have been invaluable in defining the parameters of the B-cell antibody response to different types of antigens. However, these antigens also are now known to differ in a significant manner from bona fide physiological pathogens, and precisely how these different B-cell subsets divide labor in the primary humoral immune defense of pathogens is less well understood. While there are no absolutes in this area, there are recurring themes that divide the roles of B-cell subsets to different arms of the antibody response. This review provides an overview of rules that govern the B-cell labor roles, exceptions that break these rules, and models that have been used to define them.

Fig. 1

Humoral immunity to pathogen exposure is accomplished by a division of labor between B-cell populations. Humoral immune control of pathogens is composed of three arms of antibody responses that are depicted as a function of the kinetics and magnitude of the response. Natural IgM composes the innate arm and is derived from B-1a cells prior to antigen exposure. Bridge immunity encompasses rapid TI-2 antibody responses predominantly derived from MZ B and B-1 cells. Slower adaptive humoral responses are largely contributed by FO B cells and characterized by highly matured antibodies generated in germinal centers through somatic hypermutation, affinity maturation, and class-switch recombination