B-Cell Outgrowth and Ligand-Specific Production of IL-10 Correlate with Th2 Dominance in Certain Parasitic Diseases V. PALANIVEL,* ,1 C. POSEY,* A. M. HORAUF,² W. S OLBACH,‡ W. F. PIESSENS,* AND D. A. HARN* *Department of Tropical Public Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, U.S.A.; ²Bernhard-Nocht-Institut Fur Tropenmedizin, Bernhard-Nocht-Strasse 74, Hamburg, Germany; and ‡Institut Fur Klinische Mikrobiologie, Universitat Erlangen, Erlangen, Germany PALANIVEL, V., POSEY, C., HORAUF, A. M., SOLBACH, W., PIESSENS, W. F., AND HARN, D. A. 1996. B-cell outgrowth and ligand-specific production of IL-10 correlate with Th2 dominance in certain parasitic diseases. Experimental Parasitology 84, 168–177. In many parasitic infections, dominant T helper cell (Th) type-2 CD4 + T cell responses exacerbate the disease. We have previously demon- strated that lacto-N-fucopentaose-III (LNFPIII), a sugar found on soluble egg antigens (SEA) of Schistosoma mansoni, stimulates splenic B cells from parasite-infected mice to proliferate and pro- duce IL-10, a cytokine that promotes the generation of Th2 immune responses. In the present study, we extend our observations on ligand-specific activation of IL-10 producing B cells to leishmaniasis and lymphatic filariasis. We report here that infection with Leishmania major increases the splenic B220 + B cell subset in BALB/c mice, but not BALB/c. xid (lacking B-1 cells and carrying defective B-2 cells). In addition, these B cells secrete large amounts of IL-10 in vitro in response to stimulation with soluble leishmanial extract (LSE), LNFPIII, or SO4-Lewis x . We also observed that injection of LSE increased the level of peritoneal exudate (PeC) B-1 cells (CD5 + B220 + ) in BALB/c mice, but not C57BL/6, as compared to buffer-injected controls. Further, LSE elicited PeC B cells secreted IL-10 in response to LSE as well as to the sugars tested. A similar differential secretion of IL-10 by splenic B cells from BALB/c and BALB/c.xid was seen after S. mansoni infection. Likewise, injection of soluble microfilarial extract (MFX) resulted in an increase in percentage of PeC B-1 cells in BALB/c mice, but not C57BL/6, and these cells secreted IL-10 in response to stimulation with MFX or phosphorylcholine (PC). Collectively, these results suggest a correlation between expansion of li- gand-specific IL-10 producing B and B-1 cells with dominance of Th2-type T cells in mice with the susceptible phenotype for these diseases. © 1996 Academic Press, Inc. INDEX DESCRIPTORS AND ABBREVIATIONS: B Lymphocytes; Oligosaccharides; IL-10; Parasites; Th2 response; LNFPIII, lacto-N-fucopentaose III; LNT, lacto-N-neotetraose; SEA, soluble egg antigens; LSE, soluble leishmanial extract; MFX, soluble microfilarial extract; PC, phosphorylcholine; PeC, peritoneal exudate cells. INTRODUCTION Experimental infection of mice with para- sites, such as Schistosoma mansoni and Leish- mania major, often leads to generation of mu- tually exclusive Th cell subsets. The particular Th subset which becomes dominant is depen- dent on the mouse strain. Generally, mouse strains with susceptible phenotypes tend to se- crete IL-4 and IL-10 (Th2-type), whereas re- sistant strains produce IL-2 and IFN- (Th1- type) cytokines (Bogdan et al. 1993; Reed and Sher 1995). In L. major-infected BALB/c mice, expan- sion of IL-4 producing Th2 cells is correlated with susceptibility, whereas differentiation of IFN- producing Th1 cells is observed in resis- tant C57BL/6 mice (Bogdan et al. 1993). Al- though it has not been demonstrated in a rodent model, peripheral blood mononuclear cells (PBMC) from microfilaraemic patients infected with parasites (Wuchereria bancrofti and Bru- gia malayi) show a depressed Th1-type re- sponse coincident with a sustained Th2 re- sponse, mediated via IL-10 (Mahanty and Nut- man 1995). In murine schistosomiasis, Th2 dominance associated with IL-4 and IL-10 is 1 To whom correspondence should be addressed at the Department of Tropical Public Health, Harvard School of Public Health, 665 Huntington Avenue, Building 1, Room 402, Boston, MA 02115. Fax: (617)738-4914. EXPERIMENTAL PARASITOLOGY 84, 168–177 (1996) ARTICLE NO. 0102 168 0014-4894/96 $18.00 Copyright © 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.