Skip to main content

Advertisement

SpringerLink
Log in

Metabolic changes during B cell differentiation for the production of intestinal IgA antibody

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

To sustain the bio-energetic demands of growth, proliferation, and effector functions, the metabolism of immune cells changes dramatically in response to immunologic stimuli. In this review, I focus on B cell metabolism, especially regarding the production of intestinal IgA antibody. Accumulating evidence has implicated not only host-derived factors (e.g., cytokines) but also gut environmental factors, including the possible involvement of commensal bacteria and diet, in the control of B cell metabolism during intestinal IgA antibody production. These findings yield new insights into the regulation of immunosurveillance and homeostasis in the gut.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pearce EL, Pearce EJ (2013) Metabolic pathways in immune cell activation and quiescence. Immunity 38:633–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mathis D, Shoelson SE (2011) Immunometabolism: an emerging frontier. Nat Rev Immunol 11:81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Buck MD, O’Sullivan D, Pearce EL (2015) T cell metabolism drives immunity. J Exp Med 212:1345–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. O’Neill LA, Pearce EJ (2015) Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213:15–23

    Article  PubMed  Google Scholar 

  5. Aronov M, Tirosh B (2016) Metabolic control of plasma cell differentiation- what we know and what we don’t know. J Clin Immunol 36(Suppl 1):12–17

    Article  CAS  PubMed  Google Scholar 

  6. Chang CH, Pearce EL (2016) Emerging concepts of T cell metabolism as a target of immunotherapy. Nat Immunol 17:364–368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mockler MB, Conroy MJ, Lysaght J (2014) Targeting T cell immunometabolism for cancer immunotherapy; understanding the impact of the tumor microenvironment. Front Oncol 4:107

    Article  PubMed  PubMed Central  Google Scholar 

  8. MacIver NJ, Michalek RD, Rathmell JC (2013) Metabolic regulation of T lymphocytes. Annu Rev Immunol 31:259–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Delgoffe GM, Powell JD (2015) Sugar, fat, and protein: new insights into what T cells crave. Curr Opin Immunol 33:49–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Frauwirth KA et al (2002) The CD28 signaling pathway regulates glucose metabolism. Immunity 16:769–777

    Article  CAS  PubMed  Google Scholar 

  11. Michalek RD et al (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186:3299–3303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ray JP et al (2015) The Interleukin-2-mTORc1 kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells. Immunity 43:690–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Porta C, Riboldi E, Ippolito A, Sica A (2015) Molecular and epigenetic basis of macrophage polarized activation. Semin Immunol 27:237–248

    Article  CAS  PubMed  Google Scholar 

  14. Jha AK et al (2015) Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:419–430

    Article  CAS  PubMed  Google Scholar 

  15. Doughty CA et al (2006) Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth. Blood 107:4458–4465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dufort FJ et al (2007) Cutting edge: IL-4-mediated protection of primary B lymphocytes from apoptosis via Stat6-dependent regulation of glycolytic metabolism. J Immunol 179:4953–4957

    Article  CAS  PubMed  Google Scholar 

  17. Caro-Maldonado A et al (2014) Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells. J Immunol 192:3626–3636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gutzeit C, Magri G, Cerutti A (2014) Intestinal IgA production and its role in host-microbe interaction. Immunol Rev 260:76–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brandtzaeg P (2010) Function of mucosa-associated lymphoid tissue in antibody formation. Immunol Investig 39:303–355

    Article  CAS  Google Scholar 

  20. Macpherson AJ, Koller Y, McCoy KD (2015) The bilateral responsiveness between intestinal microbes and IgA. Trends Immunol 36:460–470

    Article  CAS  PubMed  Google Scholar 

  21. Kunisawa J, Kurashima Y, Kiyono H (2012) Gut-associated lymphoid tissues for the development of oral vaccines. Adv Drug Deliv Rev 64:523–530

    Article  CAS  PubMed  Google Scholar 

  22. Ohno H (2016) Intestinal M cells. J Biochem 159:151–160

    Article  CAS  PubMed  Google Scholar 

  23. Bekiaris V, Persson EK, Agace WW (2014) Intestinal dendritic cells in the regulation of mucosal immunity. Immunol Rev 260:86–101

    Article  CAS  PubMed  Google Scholar 

  24. Gohda M et al (2008) Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer’s patches for intestinal IgA responses. J Immunol 180:5335–5343

    Article  CAS  PubMed  Google Scholar 

  25. Mora JR et al (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:1157–1160

    Article  CAS  PubMed  Google Scholar 

  26. Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K (2010) Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annu Rev Immunol 28:243–273

    Article  CAS  PubMed  Google Scholar 

  27. Kunisawa J et al (2007) Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production. Blood 109:3749–3756

    Article  CAS  PubMed  Google Scholar 

  28. Tsuji M et al (2008) Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29:261–271

    Article  CAS  PubMed  Google Scholar 

  29. Kunisawa J et al (2015) Mode of bioenergetic metabolism during B cell differentiation in the intestine determines the distinct requirement for vitamin B1. Cell Rep 13:122–131

    Article  CAS  PubMed  Google Scholar 

  30. Patke A, Mecklenbrauker I, Erdjument-Bromage H, Tempst P, Tarakhovsky A (2006) BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism. J Exp Med 203:2551–2562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Otipoby KL et al (2008) BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells. Proc Natl Acad Sci USA 105:12435–12438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Woodland RT et al (2008) Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood 111:750–760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vander Heiden MG et al (2011) Metabolic pathway alterations that support cell proliferation. Cold Spring Harb Symp Quant Biol 76:325–334

    Article  CAS  PubMed  Google Scholar 

  34. Dufort FJ et al (2014) Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for atp-citrate lyase in lipopolysaccharide-induced differentiation. J Biol Chem 289:7011–7024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pollizzi KN, Powell JD (2014) Integrating canonical and metabolic signalling programmes in the regulation of T cell responses. Nat Rev Immunol 14:435–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu C, Chapman NM, Karmaus PW, Zeng H, Chi H (2015) mTOR and metabolic regulation of conventional and regulatory T cells. J Leukoc Biol 97:837–847

  37. Kopf H, de la Rosa GM, Howard OM, Chen X (2007) Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol 7:1819–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Delgoffe GM et al (2009) The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30:832–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Delgoffe GM et al (2011) The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 12:295–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang S et al (2013) B cell-specific deficiencies in mTOR limit humoral immune responses. J Immunol 191:1692–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Benhamron S, Pattanayak SP, Berger M, Tirosh B (2015) mTOR activation promotes plasma cell differentiation and bypasses XBP-1 for immunoglobulin secretion. Mol Cell Biol 35:153–166

    Article  PubMed  Google Scholar 

  42. Lamichhane A, Kiyono H, Kunisawa J (2013) Nutritional components regulate the gut immune system and its association with intestinal immune disease development. J Gastroenterol Hepatol 28(Suppl 4):18–24

    Article  CAS  PubMed  Google Scholar 

  43. Kunisawa J, Kiyono H (2016) Sphingolipids and epoxidized lipid metabolites in the control of gut immunosurveillance and allergy. Front Nutr 3:3

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kunisawa J, Kiyono H (2015) Vitamins mediate immunological homeostasis and diseases at the surface of the body. Endocr Metab Immune Disord Drug Targets 15:25–30

    Article  CAS  PubMed  Google Scholar 

  45. Kunisawa J, Kiyono H (2013) Vitamin-mediated regulation of intestinal immunity. Front Immunol 4:189

    Article  PubMed  PubMed Central  Google Scholar 

  46. Frank RA, Leeper FJ, Luisi BF (2007) Structure, mechanism and catalytic duality of thiamine-dependent enzymes. Cell Mol Life Sci 64:892–905

    Article  CAS  PubMed  Google Scholar 

  47. Webb ME, Marquet A, Mendel RR, Rebeille F, Smith AG (2007) Elucidating biosynthetic pathways for vitamins and cofactors. Nat Prod Rep 24:988–1008

    Article  CAS  PubMed  Google Scholar 

  48. Kunisawa J, Nochi T, Kiyono H (2008) Immunological commonalities and distinctions between airway and digestive immunity. Trends Immunol 29:505–513

    Article  CAS  PubMed  Google Scholar 

  49. Randall TD (2010) Bronchus-associated lymphoid tissue (BALT) structure and function. Adv Immunol 107:187–241

    Article  CAS  PubMed  Google Scholar 

  50. Weinstein PD, Cebra JJ (1991) The preference for switching to IgA expression by Peyer’s patch germinal center B cells is likely due to the intrinsic influence of their microenvironment. J Immunol 147:4126–4135

    CAS  PubMed  Google Scholar 

  51. Kunisawa J et al (2013) Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice. Nat Commun 4:1772

    Article  PubMed  PubMed Central  Google Scholar 

  52. Galli C, Calder PC (2009) Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review. Ann Nutr Metab 55:123–139

    Article  CAS  PubMed  Google Scholar 

  53. Margioris AN (2009) Fatty acids and postprandial inflammation. Curr Opin Clin Nutr Metab Care 12:129–137

    Article  CAS  PubMed  Google Scholar 

  54. Arita M (2012) Mediator lipidomics in acute inflammation and resolution. J Biochem 152:313–319

    Article  CAS  PubMed  Google Scholar 

  55. Jin C, Flavell RA (2013) Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol 132:287–294

    Article  CAS  PubMed  Google Scholar 

  56. Kunisawa J et al (2014) Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism. J Immunol 193:1666–1671

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author’s work featured in this review article was supported by grants from MEXT/JSPS KAKENHI Grant Numbers 26293111, 16H01373, and 15H05790; from The Ministry of Health, Labour and Welfare (MHLW) and the Research on Development of New Drugs, the Japan Agency for Medical Research and Development (AMED); the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries, and Food Industry; Astellas Foundation for Research on Metabolic Disorders, Terumo Foundation for Life Sciences and Arts and Suzuken Memorial Foundation.

Author information

Authors and Affiliations

  1. Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan

    Jun Kunisawa

  2. Division of Mucosal Immunology, Department of Microbiology and Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Jun Kunisawa

  3. Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, Graduate School of Dentistry, Osaka University, Osaka, 565-0871, Japan

    Jun Kunisawa

  4. Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Jun Kunisawa

Authors
  1. Jun Kunisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Kunisawa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kunisawa, J. Metabolic changes during B cell differentiation for the production of intestinal IgA antibody. Cell. Mol. Life Sci. 74, 1503–1509 (2017). https://doi.org/10.1007/s00018-016-2414-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2414-8

Keywords

Search

Navigation