Autocrine secretion of interferon gamma negatively regulates homing of immature B cells

J Exp Med. 2000 Nov 6;192(9):1381-8. doi: 10.1084/jem.192.9.1381.

Abstract

The mechanism by which immature B cells are sequestered from encountering foreign antigens present in lymph nodes or sites of inflammation, before their final maturation in the spleen, has not been elucidated. We show here that immature B cells fail to home to the lymph nodes. These cells can actively exclude themselves from antigen-enriched sites by downregulating their integrin-mediated adhesion to the extracellular matrix protein, fibronectin. This inhibition is mediated by interferon gamma secretion. Perturbation of interferon gamma activity in vivo leads to the homing of immature B cells to the lymph nodes. This is the first example of autocrine regulation of immune cell migration to sites of foreign antigen presentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chemotaxis, Leukocyte / drug effects*
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Fibronectins / metabolism
  • Flow Cytometry
  • Integrins / metabolism
  • Interferon-gamma / metabolism*
  • Interferon-gamma / pharmacology*
  • Interleukins / pharmacology
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Culture Media, Conditioned
  • Fibronectins
  • Integrins
  • Interleukins
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate