Recombinant murine IL-5 induces high rate IgA synthesis in cycling IgA-positive Peyer's patch B cells

J Immunol. 1988 Sep 15;141(6):2035-42.

Abstract

Recent studies have shown that purified IL-5 from T cell lines and clones enhances IgA synthesis in LPS-triggered splenic B cell cultures, and that this effect is augmented by IL-4. In this study we have examined the ability of rIL-5 and rIL-4 to support spontaneous Ig synthesis in normal Peyer's patch (PP) B cell cultures. The rIL-4 supported proliferation of the HT-2 and in vivo adapted BCL-1 cell lines, increased Ia expression on normal spleen B cells, co-stimulated splenic B cell proliferation in the presence of anti-mu and enhanced IgG1 synthesis in LPS triggered splenic B cell cultures. The rIL-5 supported BCL-1 proliferation, co-stimulated splenic B cell proliferation in the presence of dextran sulfate, and increased IgA synthesis in LPS-stimulated splenic B cell cultures. Markedly enhanced IgA responses occurred in PP B cell, but not splenic B cell cultures supplemented with rIL-5 in the absence of an added B cell trigger. However, rIL-4 alone did not enhance IgA synthesis or increase the IgA synthesis of PP B cell cultures stimulated with rIL-5. The rIL-5 receptive PP B cells were present in the blast cell subpopulation, inasmuch as a low density fraction isolated on Percoll gradients accounted for the enhanced IgA synthesis. Further, cell cycle analysis of whole PP B cells using propidium iodide in conjunction with staining for surface B220, demonstrated that approximately 12 to 16% of the B cells were in the S and G2/M stages of cell cycle, the remainder being in Go + G1. The surface IgM+ B cells were predominantly in Go + G1, whereas the sIgA+ B cell subpopulation was enriched for cells in the S and G2/M compartments. The PP B cell subset responsible for enhanced IgA synthesis in the presence of rIL-5 was sIgA-positive because FACS-depletion of the sIgA+ B cells resulted in the total loss of rIL-5 enhanced IgA synthesis. Further, when PP B cells were enriched for sIgA+ B cells by cell sorting, these cells responded to rIL-5 with increased IgA synthesis in a dose-dependent manner. When the actual numbers of IgA secreting cells were assessed in PP B cell cultures with supplemental rIL-5, no significant increase in total IgA-producing cells was noted when compared with B cells cultured without rIL-5.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / classification
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Cycle / drug effects*
  • Cell Separation
  • Humans
  • Immunoglobulin A / biosynthesis*
  • Interleukin-4
  • Interleukin-5
  • Interleukins / pharmacology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Peyer's Patches / cytology*
  • Phenotype
  • Receptors, Antigen, B-Cell
  • Recombinant Proteins / pharmacology

Substances

  • Immunoglobulin A
  • Interleukin-5
  • Interleukins
  • Receptors, Antigen, B-Cell
  • Recombinant Proteins
  • Interleukin-4