Specialization and Complementation of Humoral Immune Responses to Infection

The importance of specific antibodies for the clearance of and long-term resistance to many infectious pathogens has long been appreciated. Moreover, the role in these processes of the different antibody heavy chain isotypes, each tailored to induce diverse effector pathways such as those mediated by complement and Fc receptors and to promote antibody localization in distinct regions of the body, is well established. Insights into the molecular mechanism of isotype class switching showed that during an immune response B cells could change the heavy chain of the antibody they produced, without influencing the structure and specificity of the antigen-binding variable regions of this antibody (Honjo 1983). More recently, the germinal center pathway of B cell development was elucidated, in which antibody variable regions undergo extensive structural alteration via hypermutation followed by stringent phenotypic selection (Berek 1992; Kelsoe 1995). Emerging from this pathway are memory B cells and long-lived antibody-forming cells that express antigen receptors and secrete antibodies, respectively, with increased affinity and specificity for the foreign antigen. Taken together, these findings led to a view of the acquisition of antibody-mediated resistance to infectious pathogens in mammals that involved extensive somatic matu- tion of antibody heavy and variable region structure and function during the immune response. This was in keeping with the concept that the B cell compartment comprises a major arm of the adaptive immune system. Such a view was reinforced by molecular analyses of antiviral antibody responses (Zinkernagel 1996).

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Klappentext

In recent years the results of past studies on T cell dependent and T cell independent antibody responses have coalesced with discoveries regarding the roles of various primary B cell subsets and components of the innate immune system in conferring resistance to infectious pathogens. As a consequence, a new and more complete understanding of how antibody-mediated resistance to pathogens is elaborated has emerged. The recent explosion of knowledge of Toll-like receptor specificity and function has further embellished this understanding. It is now clear that there is not only extensive overlap and cross-complementarity in the action of innate and adaptive immune systems, but also specialization of function of the various B cell subsets and the types of antibodies they produce. This synergistic interaction of multiple components of these systems is perhaps best exemplified in antibody responses to bacteria. Contributions to this monograph were chosen to highlight this new perspective on antibody responses to infection, as well as to convey its practical implications, such as for contemporary vaccine design.

Inhalt
Pattern Recognition by B Cells: The Role of Antigen Repetitiveness Versus Toll-Like Receptors.- The Multifunctional Role of Antibodies in the Protective Response to Bacterial T Cell-Independent Antigens.- B Cell Lineage Contributions to Antiviral Host Responses.- The Important and Diverse Roles of Antibodies in the Host Response to Borrelia Infections.- A Distinct Role for B1b Lymphocytes in T Cell-Independent Immunity.- Secretory Immunity Following Mutans Streptococcal Infection or Immunization.