Disrupted B-lymphocyte development and survival in interleukin-2-deficient mice

Immunology. 2001 Oct;104(2):127-34. doi: 10.1046/j.1365-2567.2001.01308.x.

Abstract

Interleukin-2-deficient (IL-2-/-) mice develop a spontaneous, progressive, CD4+ T-cell-mediated colitis with an age-related decrease in the number of B lymphocytes. The aim of this study was to determine the mechanisms of B-cell loss in IL-2-/- mice. Serum immunoglobulin G1 (IgG1) levels in 8-week-old IL-2-/- mice were above normal but then decreased dramatically with advancing age. Between 8 and 11 weeks of age, the number of B-cell progenitors (B220+ IgM-) in the bone marrow of IL-2-/- mice was less than half of those in IL-2+/+ littermates. By 22 weeks of age, very few progenitor cells remained in the bone marrow of most mice, and spleens were almost devoid of B cells. Likewise, B1 cells were not present in the peritoneal cavity of aged IL-2-/- mice. Flow cytometry analysis of B-cell differentiation in the bone marrow suggested a progressive loss of B cells from the most mature to the least mature stages, which was not dependent on IL-2 receptor-alpha (IL-2Ralpha) expression. B cells transferred from normal animals had similar survival rates in IL-2-/- and wild-type mice. We conclude that conventional B cells in older IL-2-/- mice are lost by attrition owing to a derangement in B-cell development. Because B1 cells are less dependent on the bone marrow, a separate mechanism for their loss is suggested.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ascitic Fluid / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / immunology
  • Cell Differentiation / immunology
  • Cell Survival / immunology
  • Flow Cytometry
  • Hematopoietic Stem Cells / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / blood
  • Interleukin-2 / deficiency
  • Interleukin-2 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology

Substances

  • Immunoglobulin G
  • Interleukin-2