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Functional dissection of the cytoplasmic subregions of the interleukin‐5 receptor α chain in growth and immunoglobulin G1 switch recombination of B cells
Author(s) -
Moon B.G.,
Yoshida T.,
Shiiba M.,
Nakao K.,
Katsuki M.,
Takaki S.,
Takatsu K.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01196.x
Subject(s) - biology , microbiology and biotechnology , mutant , enhancer , transgene , cytoplasm , b cell , immunoglobulin class switching , cell growth , antibody , gene , gene expression , genetics
Summary The interleukin‐5 receptor α chain (IL‐5Rα) is known to regulate the development and function of B cells and eosinophils. Although the functions of IL‐5Rα cytoplasmic domain subregions have been studied extensively using cultured cell lines, this approach has limitations when studying the functions of distinct primary B‐cell subpopulations and their responsiveness to IL‐5. In the present study, we generated mice on an IL‐5Rα null background, each expressing a mutant form of an IL‐5Rα transgene ligated to a µ enhancer and VH promoter, either lacking the cytoplasmic DC3 region or substituting two proline residues for alanine (ApvA) in the membrane‐proximal ppvp motif of the cytoplasmic domain. The ppvp motif, which mediates activation of JAK2/STAT5 and Btk, also contributes to c‐fos , c‐jun and c‐myc expression. IL‐5Rα null mutant mice showed impaired B‐1‐cell development, reduced serum immunoglobulin G3 (IgG3) and IgM, no IL‐5‐induced enhancement of B‐cell proliferation and IL‐5‐induced switch recombination from the µ gene to γ1 gene; these were not recovered following the expression of the ApvA mutant. In contrast, absence of the DC3 region affected the IL‐5‐induced switch recombination from the µ to the γ1 gene and B‐1‐cell development, while IL‐5‐induced proliferation and IgM production were at levels similar to those of B cells expressing wild‐type IL‐5Rα transgene. The results clearly indicated that the ppvp motif and the DC3 region of IL‐5Rα played distinct roles in B‐cell proliferation and differentiation. Thus, this present approach offers new insights into the functions of the cytoplasmic subregions of IL‐5Rα, in particular its carboxy‐terminal region.