Differential impact of Toll-like receptor signaling on distinct B cell subpopulations

Abstract

B cells exhibit a range of functional responses following TLR engagement including immunoglobulin and cytokine production, proliferation, antigen presentation and migration. However, B cell intrinsic TLR responses appear to be precisely programmed based upon the developmental stage of the cell. B cell subpopulations classified as innate immune cells including marginal zone and B-1 B cells exhibit robust responses to TLR stimulation. In contrast, activation of other B cell subsets is constrained via a variety of developmentally regulated events. In this review we provide an overview of TLR responses in murine and human B cells and specifically highlight patterns of TLR expression and developmentally regulated functional responses.

Figure 1

Characteristic markers for developmental B cell subpopulations. Schematic depiction of B cell subsets during B cell development and their characteristic phenotypic markers as mentioned in the text in both mouse and human. No well established markers exist for murine memory B cells or human marginal zone B cells.

Figure 2

Functional responses of splenic marginal zone B cells to Toll-like receptor engagement. MZ B cells are generally considered as belonging to the innate immune system. They are the main players during T cell-independent immune responses and are crucial during the early phase of immune responses. Consistent with their characterization as innate immune cells MZ B cells exhibit multiple functional responses to TLR stimulation. They rapidly can start to proliferate and secrete immunoglobulins and cytokines. Up-regulation of BAFF receptors can result in prolonged survival. Through modulation of integrins on their surface MZ B cells can leave the marginal zone and migrate to different locations. Finally, MZ B cells can act as professional antigen presenting cells, thereby providing efficient T cell help.