Neuroimmune modulation of lymphocyte function--I. Substance P enhances immunoglobulin synthesis in lipopolysaccharide activated murine splenic B cell cultures.
Murine B cells have been shown to possess substance P (SP) receptors, but their functional and biological significance remains unresolved. While previous studies have suggested that SP can induce B cells to secrete Ig, the effect could be indirect since mixed cultures were used. In order to assess directly the ability of SP to trigger normal B cells, we have studied the effects of this neuropeptide on purified splenic B cells in vitro. Although an activation, e.g. lipopolysaccharide (LPS), was required, the functionality of the B cell SP receptors was clearly shown by the ability of subnanomolar concentrations of this neuropeptide to augment antibody secretion in a dose-dependent fashion. Specifically, IgM and IgG levels, determined by an isotype-specific sandwich ELISA, were greatly enhanced at 10(-10) M SP by as much as 500 and 572% respectively, while IgA levels were only modestly affected. Even picomolar concentrations of SP could significantly increase IgM levels. This observed enhancement of Ig production was SP specific since B cells co-cultured in the presence of excess SP antagonist were reduced to basal LPS-stimulated Ig levels. Furthermore, this synergistic stimulation by SP and LPS upon normal B cells could not be attributed to SP-induced cell proliferation since stimulatory concentrations of SP were not mitogenic and at high concentrations could inhibit cell proliferation. Rather, it was observed that the increased IgM and IgG secretion was in part attributable to a greater number of B cells secreting antibodies as demonstrated with an ELISPOT assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Pascual
D W
DW
Department of Oral Biology, University of Alabama, Birmingham 35294.
McGhee
J R
JR
Kiyono
H
H
Bost
K L
KL
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D013373:Substance P / Q000096:biosynthesis*
D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; D013373:Substance P; D004247:DNA