B cells that produce immunoglobulin E mediate colitis in BALB/c mice

Gastroenterology. 2012 Jan;142(1):96-108. doi: 10.1053/j.gastro.2011.09.044. Epub 2011 Oct 6.


Background & aims: Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Rα on T and B cells determines their effector functions and mediates oxazolone-induced colitis.

Methods: We studied induction of colitis with oxazolone in wild-type mice and those with CD4(+) T cells that did not express IL-4Rα (Lck(cre)IL-4Rα(-/lox)). We also generated mice with B cells that did not express IL-4Rα (mb1(cre)IL-4Rα(-/lox)) and studied induction of colitis.

Results: Lck(cre)IL-4Rα(-/lox) mice did not develop colitis in response to oxazolone, and their levels of IL-4, IL-13, and immunoglobulin (Ig) E were reduced. Adoptive transfer of naïve, wild-type CD4(+) Th cells depleted of natural killer T cells to Lck(cre)IL-4Rα(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-4Rα(-/lox) mice maintained their protection against colitis when IL-13-deficient CD4(+) T cells were transferred. These findings indicate that development of colitis involves not only natural killer T-cell functions, but also requires IL-13 production by CD4(+) T helper cells. Mb1(cre)IL-4Rα(-/lox) mice, which cannot produce IgE, were also protected against oxazolone-induced colitis. Blocking IgE binding significantly reduced mast cell numbers in colons and protected wild-type BALB/c mice from the onset of colitis.

Conclusions: IL-4 appears to induce CD4(+) Th2 cells to produce IL-13 and B cells to produce IgE, which together mediate oxazolone-induced colitis in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / immunology*
  • Colon / pathology
  • Disease Models, Animal
  • Disease Susceptibility
  • Immunoglobulin E / metabolism*
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Male
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Natural Killer T-Cells / immunology
  • Oxazolone
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Signal Transduction
  • Th2 Cells / immunology
  • Th2 Cells / transplantation
  • Time Factors


  • Antibodies, Neutralizing
  • Il4ra protein, mouse
  • Interleukin-13
  • Receptors, Cell Surface
  • Oxazolone
  • Interleukin-4
  • Immunoglobulin E