Induction of human B cell differentiation by Fc region activators. II. Stimulation of IL-6 production.
Fc region fragments derived from the enzymatic cleavage of human IgG have been shown to induce human peripheral blood-derived B cells to differentiate into Ig secreting cells (ISC). The synthetic peptide p23, corresponding to residues 335 to 357 in the Fc region of human IgG1, represents a region of the molecule responsible for stimulation of ISC formation. Fc region-induced ISC formation requires at least two signals; one supplied by Fc region activators and one supplied by a T cell-derived factor(s). In this report we show that the coculture of human PBMC with pFc' or p23, results in the release of factor(s) that resemble IL-6 in its pattern of biologic activity. This conclusion is based on the observations that supernatants from Fc region-stimulated PBMC cultures contained increased levels of elements that scored as positive in two assays for IL-6: the B9.9 hybridoma growth and the CESS cell differentiation assays. Moreover, RNA from Fc region-stimulation PBMC contained increased levels of IL-6 cDNA-hybridizable elements. Finally, it was observed that rabbit anti-IL-6 inhibited the ability of supernatants derived from Fc region-stimulated PBMC cultures to induce B9.9 cell proliferation as well as p23-induced ISC formation in intact PBMC cultures. Fc region fragments induce both monocytes and T cells to produce IL-6. Taken together, these results indicate that IL-6 is produced in Fc region-stimulated PBMC cultures and is involved in B cell activation by these activators.
Morgan
E L
EL
Division of Cellular Immunology, Immunetech Pharmaceuticals, San Diego, CA 92121.
Hobbs
M V
MV
Thoman
M L
ML
Janda
J
J
Noonan
D J
DJ
Kadar
J
J
Weigle
W O
WO
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D015152:Blotting, Northern; D002454:Cell Differentiation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics
D007141:Immunoglobulin Fc Fragments; D007376:Interleukin-2; D015850:Interleukin-6; D009842:Oligopeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D015847:Interleukin-4