Enhancement of humoral immunity by interleukin-12.
We have found that IL-12 treatment of mice leads to long-lasting enhancement in production of most antibody isotypes in conventional B-cell responses. Initial recruitment of new B-cell clones into the response is mediated by IFN-gamma, but subsequent enhancement of Ig secretion appears to be IFN-gamma-independent. We have further found that activated B cells can directly bind IL-12. Taken together, our results suggest a two-step model for the role of IL-12 in enhancement of humoral immunity. Initially, IL-12 induces production of IFN-gamma from Th1 and NK cells. Enough cytokine can be produced from either cell type to then mediate gamma 2a heavy chain isotype switching as well as temporary suppression of IgG1 production. IL-12 further stimulates post-switched cells, including cells producing IgG1, to secrete greatly increased amounts of antibody. This step is not mediated by IFN-gamma but might be due to direct IL-12 binding to activated B lymphocytes. Depletion of B1 cells by IL-12 may further enhance antibody responsiveness since B1 cells are known to competitively inhibit Ig secretion by conventional B cells. The end result is that IL-12 causes a generalized upregulation in production of all antibodies and therefore acts as a strong adjuvant for humoral as well as cellular immunity.
Metzger
D W
DW
Department of Microbiology, Medical College of Ohio, Toledo 43699-0008, USA.
Buchanan
J M
JM
Collins
J T
JT
Lester
T L
TL
Murray
K S
KS
Van Cleave
V H
VH
Vogel
L A
LA
Dunnick
W A
WA
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018664:Interleukin-12; D009113:Muramidase