Abstract

B cell activation and antibody production against foreign antigens is a central step of host defense. This is achieved via highly regulated multi-phase processes that involve a variety of cells of both innate and adaptive arms of the immune system. MHC class II-restricted CD4+ T cells specific for peptide antigens, which acquire professional follicular B cell helper functions, have been long recognized as key players in this process. Recent data, however, challenge this paradigm by showing the existence of other helper cell types. CD1d restricted NKT cells specific for lipid antigens are one such new player and can coopt bona fide follicular helper phenotypes. Their role in helping antigen-specific B cell response to protein antigens, as well as to the so called “help-less” antigens that cannot be recognized by T follicular helper cells, is being increasingly elucidated, highlighting their potential pathophysiological impact on the immune response, as well as on the design of improved vaccine formulations.

Highlights

  • CD4+ T cells that are specific for peptides presented by MHC class II

  • Upon mice immunization with αGalCer, iNKT follicular helper (iNKTFH) cells expand more in CD4+ T cell-deficient than in WT mice [62], suggesting that in physiological conditions, the presence of T follicular helper (TFH) cells might somewhat compete with iNKTFH cells

  • Formation, affinity maturation and memory response. These results have suggested that iNKTFH cells may be less efficient than the TFH ones in promoting Germinal Centers (GC) and B cell memory formation

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Summary

Introduction

CD4+ T cells that are specific for peptides presented by MHC class II It became clear that CD1d-restricted natural killer T (NKT) cells, a subset of lipid-specific T lymphocytes that display innate-effector functions, can help B cell responses [3]. Both CD4+ T and Antibodies 2015, 4. NKT cells coopt the follicular helper pathway that is critical to determining the T cell contribution; this results in distinct outcomes for antibody responses and implies complementary functions relevant both for host protection and vaccine design

T Dependent Antibody Responses
T Independent Antibody Responses
CD1d-Restricted Natural Killer T Cells
Cognate iNKT Cell Help for B Cells
Distinct Dynamics of B Cell Response Helped by iNKTFH Cells
Non-Cognate iNKT Cell Help for B Cells
10. Type 2 NKT Cell Help to B Cells
11. Concluding Remarks
Conflicts of Interest

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