How Do Natural Killer T Cells Help B Cells?

Overview

Journal Expert Rev Vaccines

Date 2009 Jul 25

PMID 19627191

Citations 22

Authors

Mark L Lang

Affiliations

Soon will be listed here.

Abstract

CD1d-restricted natural killer (NKT) cells are important contributors to antigen-specific antibody responses. There is, therefore, considerable interest in the design and implementation of strategies to appropriately activate NKT cells and boost vaccine-induced protective antibody responses. In order to achieve these goals, investigators are examining the mechanisms by which NKT cells enhance antibody responses. Although information is limited, it is now appreciated that both cognate and noncognate interactions between CD1d-expressing B cells and NKT cells drive enhanced antibody responses. NKT cells may provide B-cell help in the form of direct receptor-mediated interactions as well as by secretion of soluble effectors, including cytokines. In this article, we review the evidence in support of these mechanisms and discuss how they likely take place in the context of interactions of NKT cells with other cell types, such as dendritic cells and helper T cells. We also discuss the evidence that NKT cells affect discrete differentiation events in the multistep process by which a naive B cell experiences antigen and develops into a memory B cell or an antibody-secreting plasma cell. Since most information on NKT cells and humoral immunity has been derived from murine studies, we discuss what is known about human NKT cells and humoral immunity. We offer thoughts on whether the findings in murine systems will translate to humans.

Citing Articles

Identification and validation of depression-associated genetic variants in the UK Biobank cohort with transcriptome and DNA methylation analyses in independent cohorts.

Lafta M, Sokolov A, Rukh G, Schioth H Heliyon. 2025; 11(2):e41865.

PMID: 39897774 PMC: 11787470. DOI: 10.1016/j.heliyon.2025.e41865.

Lysosomal processing of sulfatide analogs alters target NKT cell specificity and immune responses in cancer.

Nishio K, Pasquet L, Camara K, DiSapio J, Hsu K, Kato S J Clin Invest. 2023; 134(4).

PMID: 38127463 PMC: 10866642. DOI: 10.1172/JCI165281.

A Case Study to Dissect Immunity to SARS-CoV-2 in a Neonate Nonhuman Primate Model.

Fovet C, Pimienta C, Galhaut M, Relouzat F, Nunez N, Cavarelli M Front Immunol. 2022; 13:855230.

PMID: 35603150 PMC: 9114777. DOI: 10.3389/fimmu.2022.855230.

Effect of Immune Cell Infiltration on Occurrence of Pulmonary Hypertension in Pulmonary Fibrosis Patients Based on Gene Expression Profiles.

Zhu F, Zuo L, Hu R, Wang J, Yang Z, Qi X Front Med (Lausanne). 2021; 8:671617.

PMID: 34307406 PMC: 8292720. DOI: 10.3389/fmed.2021.671617.

Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder.

Yang H, Liu D, Zhao C, Feng B, Lu W, Yang X Transl Psychiatry. 2021; 11(1):225.

PMID: 33866329 PMC: 8053199. DOI: 10.1038/s41398-021-01348-0.

References

Van Es J, Meyling F, Logtenberg T . High frequency of somatically mutated IgM molecules in the human adult blood B cell repertoire. Eur J Immunol. 1992; 22(10):2761-4. DOI: 10.1002/eji.1830221046. View

Zheng X, Zhang H, Yin L, Wang C, Liu Y, Zheng P . Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon for costimulation. PLoS One. 2008; 3(7):e2703. PMC: 2442875. DOI: 10.1371/journal.pone.0002703. View

Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T . Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med. 2003; 9(5):582-8. DOI: 10.1038/nm851. View

Kenna T, Golden-Mason L, Porcelli S, Koezuka Y, Hegarty J, OFarrelly C . NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. J Immunol. 2003; 171(4):1775-9. DOI: 10.4049/jimmunol.171.4.1775. View

Tonti E, Galli G, Malzone C, Abrignani S, Casorati G, Dellabona P . NKT-cell help to B lymphocytes can occur independently of cognate interaction. Blood. 2008; 113(2):370-6. DOI: 10.1182/blood-2008-06-166249. View

Klein U, Rajewsky K, Kuppers R . Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J Exp Med. 1998; 188(9):1679-89. PMC: 2212515. DOI: 10.1084/jem.188.9.1679. View

van der Vliet H, Nishi N, de Gruijl T, von Blomberg B, van den Eertwegh A, Pinedo H . Human natural killer T cells acquire a memory-activated phenotype before birth. Blood. 2000; 95(7):2440-2. View

Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg R, Bhan A . Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002; 16(2):219-30. DOI: 10.1016/s1074-7613(02)00274-1. View

Roberts T, Sriram V, Spence P, Gui M, Hayakawa K, Bacik I . Recycling CD1d1 molecules present endogenous antigens processed in an endocytic compartment to NKT cells. J Immunol. 2002; 168(11):5409-14. DOI: 10.4049/jimmunol.168.11.5409. View

10.

Matsuda J, Naidenko O, Gapin L, Nakayama T, Taniguchi M, Wang C . Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med. 2000; 192(5):741-54. PMC: 2193268. DOI: 10.1084/jem.192.5.741. View

11.

McHeyzer-Williams L, McHeyzer-Williams M . Antigen-specific memory B cell development. Annu Rev Immunol. 2005; 23:487-513. DOI: 10.1146/annurev.immunol.23.021704.115732. View

12.

Chang W, Kim J, Kim Y, Kim Y, Lee J, Azuma M . Cutting edge: Programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy. J Immunol. 2008; 181(10):6707-10. DOI: 10.4049/jimmunol.181.10.6707. View

13.

Zajonc D, Savage P, Bendelac A, Wilson I, Teyton L . Crystal structures of mouse CD1d-iGb3 complex and its cognate Valpha14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids. J Mol Biol. 2008; 377(4):1104-16. PMC: 2579742. DOI: 10.1016/j.jmb.2008.01.061. View

14.

McHeyzer-Williams L, Cool M, McHeyzer-Williams M . Antigen-specific B cell memory: expression and replenishment of a novel b220(-) memory b cell compartment. J Exp Med. 2000; 191(7):1149-66. PMC: 2193163. DOI: 10.1084/jem.191.7.1149. View

15.

Mizuno M, Masumura M, Tomi C, Chiba A, Oki S, Yamamura T . Synthetic glycolipid OCH prevents insulitis and diabetes in NOD mice. J Autoimmun. 2004; 23(4):293-300. DOI: 10.1016/j.jaut.2004.09.008. View

16.

Gumperz J . The ins and outs of CD1 molecules: bringing lipids under immunological surveillance. Traffic. 2006; 7(1):2-13. DOI: 10.1111/j.1600-0854.2005.00364.x. View

17.

Schrantz N, Sagiv Y, Liu Y, Savage P, Bendelac A, Teyton L . The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells. J Exp Med. 2007; 204(4):841-52. PMC: 2118543. DOI: 10.1084/jem.20061562. View

18.

Chang D, Osman K, Connolly J, Kukreja A, Krasovsky J, Pack M . Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med. 2005; 201(9):1503-17. PMC: 1389847. DOI: 10.1084/jem.20042592. View

19.

Allen C, Cyster J . Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin Immunol. 2008; 20(1):14-25. PMC: 2366796. DOI: 10.1016/j.smim.2007.12.001. View

20.

Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M . A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res. 2005; 11(5):1910-7. DOI: 10.1158/1078-0432.CCR-04-1453. View