The invention includes a mouse in which the IL-21 receptor gene is disrupted by homologous recombination, the disruption being sufficient to prevent expression of the IL-21 receptor and thus to inhibit the action of IL-21. The invention also includes a mouse in which both the IL-21 receptor gene and the IL-4 gene are simultaneously disrupted in fashions being sufficient to inhibit the action of IL-21 and the production of IL-4. In a homozygous state, these mutations produce a mouse that has diminished B cell function.

This invention also relates to the use of agents that inhibit the interaction of IL-21 with the IL-21 receptor to modulate an immune response. This invention may be used to alter B cell activity, to treat a subject with Job's disorder, to treat an allergic reaction in a subject, or prevent an allergic reaction in a subject,