PIK3IP1 promotes extrafollicular class switching in T-Dependent immune responses

Kristina Ottens, Jalyn Schneider, Lawrence P. Kane, Anne B. Satterthwaite

Research output: Contribution to journalArticlepeer-review

Abstract

PI3K plays multiple roles throughout the life of a B cell. As such, its signaling is tightly regulated. The importance of this is illustrated by the fact that both loss- and gain-of-function mutations in PI3K can cause immunodeficiency in humans. PIK3IP1, also known as TrIP, is a transmembrane protein that has been shown to inhibit PI3K in T cells. Results from the ImmGen Consortium indicate that PIK3IP1 expression fluctuates throughout B cell development in a manner inversely correlated with PI3K activity; however, its role in B cells is poorly understood. In this study, we define the consequences of B cell–specific deletion of PIK3IP1. B cell development, basal Ig levels, and T-independent responses were unaffected by loss of PIK3IP1. However, there was a significant delay in the production of IgG during T-dependent responses, and secondary responses were impaired. This is likely due to a role for PIK3IP1 in the extrafollicular response because germinal center formation and affinity maturation were normal, and PIK3IP1 is not appreciably expressed in germinal center B cells. Consistent with a role early in the response, PIK3IP1 was downregulated at late time points after B cell activation, in a manner dependent on PI3K. Increased activation of the PI3K pathway was observed in PIK3IP1-deficient B cells in response to engagement of both the BCR and CD40 or strong cross-linking of CD40 alone. Taken together, these observations suggest that PIK3IP1 promotes extrafollicular responses by limiting PI3K signaling during initial interactions between B and T cells. The Journal of Immunology, 2020, 205: 2100–2108.

Original languageEnglish (US)
Pages (from-to)2100-2108
Number of pages9
JournalJournal of Immunology
Volume205
Issue number8
DOIs
StatePublished - Oct 15 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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