Recombinant murine IL-5 induces high rate IgA synthesis in cycling IgA-positive Peyer's patch B cells.
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)
Beagley
K W
KW
Department of Microbiology, University of Alabama, Birmingham, AL 35294.
Eldridge
J H
JH
Kiyono
H
H
Everson
M P
MP
Koopman
W J
WJ
Honjo
T
T
McGhee
J R
JR
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D002469:Cell Separation; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D015847:Interleukin-4; D015848:Interleukin-5; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010581:Peyer's Patches / Q000166:cytology*; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins / Q000494:pharmacology
D007070:Immunoglobulin A; D015848:Interleukin-5; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4