Intestinal protection without t cell help

Access through your institution Buy or subscribe Consider the scenario of a mouse that lacks all secondary lymphoid tissues and T cells. This mouse must co-exist with the huge biomass of

microorganisms living in the gut. Can it do this? Amazingly, yes! A landmark paper by Sidonia Fagarasan and colleagues published in 2008 revealed that isolated lymphoid follicles (ILFs) in

the gut can function as inductive sites for the generation of IgA-producing plasma cells in the absence of T cell help. This primordial mechanism for maintaining homeostasis with our

microbiota could also explain why humans with hyper-IgM syndrome, who harbour mutations in CD40 and hence have defective B cell–T cell interactions, retain intestinal IgA responses. At the

time of this publication, my lab had been puzzling over why lymphotoxin (LT)-deficient mice have a selective deficiency in IgA. Seminal findings from Reina Mebius’ group had shown that

lymphoid tissue inducer (LTi) cells are a crucial source of LTαβ that, through stimulation of LTβ receptor on stromal cells, initiates the development of lymphoid tissue anlage. Fagarasan

and colleagues made the next leap in our understanding by showing that LTαβ-expressing ‘LTi-like’ cells in the adult gut interact with gut-resident stromal cells to orchestrate T

cell-independent IgA production within ILFs. Not only did this paper provide an explanation for IgA deficiency in LT-deficient mice, but it also showed that interactions within ILFs

facilitate the proteolytic processing of transforming growth factor-β to its active form, which functions to promote antibody class switching to IgA. This is a preview of subscription

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * Tsuji, M. et al. Requirement for lymphoid tissue-inducer cells in isolated

follicle formation and T cell-independent immunoglobulin A generation in the gut. _Immunity_ 29, 261–271 (2008) Article  CAS  Google Scholar  RELATED ARTICLES * Mebius, R. E., Rennert, P.

& Weissman, I. L. Developing lymph nodes collect CD4+CD3– LTβ+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. _Immunity_ 7, 493–504 (1997)

Article  CAS  Google Scholar  * Lane, P. J. L. The architects of B and T cell immune responses. _Immunity_ 29, 171–172 (2008) Article  CAS  Google Scholar  Download references AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Department of Immunology, University of Toronto, Toronto, Ontario, Canada Jennifer L. Gommerman Authors * Jennifer L. Gommerman View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jennifer L. Gommerman. ETHICS DECLARATIONS COMPETING INTERESTS The author

declares no competing interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gommerman, J.L. Intestinal protection without T cell help. _Nat Rev

Immunol_ 20, 275 (2020). https://doi.org/10.1038/s41577-020-0280-y Download citation * Published: 29 January 2020 * Issue Date: May 2020 * DOI: https://doi.org/10.1038/s41577-020-0280-y

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