Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets.
B cells are critical players in the orchestration of properly regulated immune responses, providing protection against infectious agents without inflicting autoinflammatory damage. A balanced B cell compartment is also essential to create protective immunity in response to vaccines. This difficult compromise is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to powerfully modulate other components of the innate and adaptive immune system. For the most part, however, the necessary division of labor among different B cell populations is poorly understood. B cell dysfunction has been implicated in multiple autoimmune conditions. The physiological importance and complexity of B cell functions has been brought to the fore in recent years by the success of rituximab-based B cell depletion therapy (BCDT) in multiple autoimmune diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS) which are conventionally viewed as T-cell mediated conditions. Given the widespread utilization of BCDT in malignant and autoimmune diseases and the key role of B cells in both protective immunity and pathogenic autoimmunity, a better understanding of B cell functions is of the essence and a focus of the research in our division. We are investigating these issues through a variety of approaches, including the study of the phenotype and function of human B cell populations in health, their perturbation in autoimmune disease states, the effects of targeted biologic therapies, and the study of relevant murine models.
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, NY 14642, USA.
Jennifer H
JH
Anolik
R John
RJ
Looney
Frances E
FE
Lund
Troy D
TD
Randall
Iñaki
I
Sanz
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D018448:Models, Immunological
D016207:Cytokines