IL-4-producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8430-E8439. doi: 10.1073/pnas.1708125114. Epub 2017 Sep 15.


Interleukin-4 (IL-4)-induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major, while conferring immunity to the intestinal trematode Schistosoma mansoni Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (mb1creIL-4Rα-/lox) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated S. mansoni-induced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response. In both disease models, IL-4Rα-responsive B cells displayed increased IL-4 production as early as day 1 after infection. Together, these results demonstrate that IL-4-producing and IL-4Rα-responsive B cells are critical in regulating and assisting early T helper dichotomy toward Th2 responses, which are detrimental in cutaneous leishmaniasis but beneficial in acute schistosomiasis.

Keywords: B cells; IL-4R alpha; leishmaniasis; mouse; schistosomiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Interleukin-4 / metabolism*
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Interleukin-4 / immunology
  • Receptors, Interleukin-4 / metabolism*
  • Schistosoma mansoni / immunology
  • Schistosomiasis / immunology*
  • Schistosomiasis / parasitology
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Receptors, Interleukin-4
  • Interleukin-4