Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response

Invariant Natural Killer T (NKT) cells represent a unique subset of innate-like T cells that express both NK cell and T cell receptors. These cells are rapidly activated by glycolipid antigens presented via CD1d molecules on antigen-presenting cells (APCs), including B cells, dendritic cells (DCs),...

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Main Authors: Pablo A. Palacios, Álvaro Santibañez, Fernanda Aguirre-Muñoz, Cristián Gutiérrez-Vera, Valentina Niño de Zepeda-Carrizo, Martín Góngora-Pimentel, Marioly Müller, Mónica Cáceres, Alexis M. Kalergis, Leandro J. Carreño
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505883/full
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author Pablo A. Palacios
Álvaro Santibañez
Fernanda Aguirre-Muñoz
Cristián Gutiérrez-Vera
Valentina Niño de Zepeda-Carrizo
Martín Góngora-Pimentel
Marioly Müller
Mónica Cáceres
Alexis M. Kalergis
Leandro J. Carreño
author_facet Pablo A. Palacios
Álvaro Santibañez
Fernanda Aguirre-Muñoz
Cristián Gutiérrez-Vera
Valentina Niño de Zepeda-Carrizo
Martín Góngora-Pimentel
Marioly Müller
Mónica Cáceres
Alexis M. Kalergis
Leandro J. Carreño
author_sort Pablo A. Palacios
collection DOAJ
description Invariant Natural Killer T (NKT) cells represent a unique subset of innate-like T cells that express both NK cell and T cell receptors. These cells are rapidly activated by glycolipid antigens presented via CD1d molecules on antigen-presenting cells (APCs), including B cells, dendritic cells (DCs), and macrophages, or through cytokine-dependent mechanisms. Their ability to produce a wide range of cytokines and express costimulatory molecules underscores their critical role in bridging innate and adaptive immunity. B cells, traditionally recognized for their role in antibody production, also act as potent APCs due to their high expression of CD1d, enabling direct interactions with iNKT cells. This interaction has significant implications for humoral immunity, influencing B cell activation, class-switch recombination (CSR), germinal center formation, and memory B cell differentiation, thus expanding the conventional paradigm of T cell–B cell interactions. While the influence of iNKT cells on B cell biology and humoral responses is well-supported, many aspects of their interaction remain unresolved. Key questions include the roles of different iNKT cell subsets, the diversity of APCs, the spatiotemporal dynamics of these interactions, especially during early activation, and the potential for distinct glycolipid ligands to modulate immune outcomes. Understanding these factors could provide valuable insights into how iNKT cells regulate B cell-mediated immunity and offer opportunities to harness these interactions in immunotherapeutic applications, such as vaccine development. In this review, we examine these unresolved aspects and propose a novel perspective on the regulatory potential of iNKT cells in humoral immunity, emphasizing their promise as a target for innovative vaccine strategies.
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spelling doaj-art-6c2d32e3a1934ccfb7d18a7f52feb4952025-08-20T02:43:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15058831505883Can invariant Natural Killer T cells drive B cell fate? a look at the humoral responsePablo A. Palacios0Álvaro Santibañez1Fernanda Aguirre-Muñoz2Cristián Gutiérrez-Vera3Valentina Niño de Zepeda-Carrizo4Martín Góngora-Pimentel5Marioly Müller6Mónica Cáceres7Alexis M. Kalergis8Leandro J. Carreño9Millennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileDepartamento de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, ChileInvariant Natural Killer T (NKT) cells represent a unique subset of innate-like T cells that express both NK cell and T cell receptors. These cells are rapidly activated by glycolipid antigens presented via CD1d molecules on antigen-presenting cells (APCs), including B cells, dendritic cells (DCs), and macrophages, or through cytokine-dependent mechanisms. Their ability to produce a wide range of cytokines and express costimulatory molecules underscores their critical role in bridging innate and adaptive immunity. B cells, traditionally recognized for their role in antibody production, also act as potent APCs due to their high expression of CD1d, enabling direct interactions with iNKT cells. This interaction has significant implications for humoral immunity, influencing B cell activation, class-switch recombination (CSR), germinal center formation, and memory B cell differentiation, thus expanding the conventional paradigm of T cell–B cell interactions. While the influence of iNKT cells on B cell biology and humoral responses is well-supported, many aspects of their interaction remain unresolved. Key questions include the roles of different iNKT cell subsets, the diversity of APCs, the spatiotemporal dynamics of these interactions, especially during early activation, and the potential for distinct glycolipid ligands to modulate immune outcomes. Understanding these factors could provide valuable insights into how iNKT cells regulate B cell-mediated immunity and offer opportunities to harness these interactions in immunotherapeutic applications, such as vaccine development. In this review, we examine these unresolved aspects and propose a novel perspective on the regulatory potential of iNKT cells in humoral immunity, emphasizing their promise as a target for innovative vaccine strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505883/fulliNKT cellsglycolipidsB cellsgerminal centerclass-switch recombinationhumoral response
spellingShingle Pablo A. Palacios
Álvaro Santibañez
Fernanda Aguirre-Muñoz
Cristián Gutiérrez-Vera
Valentina Niño de Zepeda-Carrizo
Martín Góngora-Pimentel
Marioly Müller
Mónica Cáceres
Alexis M. Kalergis
Leandro J. Carreño
Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
Frontiers in Immunology
iNKT cells
glycolipids
B cells
germinal center
class-switch recombination
humoral response
title Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
title_full Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
title_fullStr Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
title_full_unstemmed Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
title_short Can invariant Natural Killer T cells drive B cell fate? a look at the humoral response
title_sort can invariant natural killer t cells drive b cell fate a look at the humoral response
topic iNKT cells
glycolipids
B cells
germinal center
class-switch recombination
humoral response
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505883/full
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