Recombinant Dirofilaria immitis polyprotein that stimulates murine B cells to produce nonspecific polyclonal immunoglobulin E antibody.
Nonspecific immunoglobulin E (IgE) production is an event characteristically observed in parasitic helminth infections, but its mechanisms are still unclear. To define these mechanisms, we prepared a recombinant Dirofilaria immitis protein (rDiAg) and assessed its effect on nonspecific IgE production. rDiAg preferentially induced nonspecific IgE production, without eliciting specific IgE production, as well as a Th2-type cytokine profile (high interleukin-4 [IL-4] and IL-10 production but low gamma interferon production) in BALB/c mice. rDiAg significantly elicited the proliferative response of naive B cells. This response was not abolished by polymyxin B, an inhibitor of lipopolysaccharide (LPS), and rDiAg normally expanded splenic B cells from LPS nonresponder C3H/HeJ mice. Thus, the mitogenic effect of rDiAg was not due to LPS contamination. rDiAg also enhanced levels of CD23 expression on splenic B cells. Splenic B cells produced marked levels of IgE when cultured with the combination of rDiAg and IL-4 (rDiAg-IL-4), whereas peritoneal B cells produced negligible levels of IgE. rDiAg-IL-4-induced IgE production by splenic B cells was synergistically increased by coculture with peritoneal B cells. rDiAg-driven IL-10 secretion was higher in peritoneal B cells than in splenic B cells. IgE production by splenic B cells cocultured with peritoneal B cells was decreased to a level comparable to that by splenic B cells in the presence of a neutralizing anti-IL-10 monoclonal antibody. Collectively, these results suggest that rDiAg-induced polyclonal expansion and IgE class switching of splenic B cells contribute to nonspecific IgE production and that these responses are enhanced by peritoneal B-cell-derived IL-10.
Tezuka
Hiroyuki
H
Section of Environmental Parasitology, Department of International Health Development, Division of Public Health, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo 113-8519, Japan.
Imai
Shinjiro
S
Muto
Riho
R
Furuhashi
Yuko
Y
Fujita
Koichiro
K
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000918:Antibody Specificity; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004183:Dirofilaria immitis / Q000276:immunology*; D005260:Female; D015801:Helminth Proteins / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology; D011817:Rabbits; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; C104085:DIPA protein, Dirofilaria immitis; D015801:Helminth Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma