EARLY INDUCTION AND AUGMENTATION OF PARASITIC ANTIGEN-SPECIFIC ANTIBODY-PRODUCING B LYMPHOCYTES IN THE NON-PEYER’S PATCH REGION OF THE SMALL INTESTINE

Ching-Hua Wang¹, Elizabeth M. Richards¹, Robert D. Block², Enio M. Lezcano¹ and Ricardo Gutierrez¹

1 Biology Department, California State university, 5500 University parkway, San Bernardino, CA 92407, USA, ² Department of Neurology and Neural Science, School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

Received 10/12/98 Accepted 10/20/98

2. INTRODUCTION

Most investigations concerning infection and induction of intestinal immune response with infectious organisms other than TS, to date, have focused on the response of IgA-producing B lymphocytes in the Peyer's patches of the small intestine (1-6). However, intestinal immune responses that take place in areas other than the Peyer's patches are only beginning to be closely studied. Likewise, the dynamics of early activation of intestinal B lymphocytes by TS have yet to be characterized. Since the non-lymphoid regions of the small intestine possess far more disseminated lymphocytes than all of the Peyer's patches combined, and antibodies of the IgG and IgE isotypes are more efficient in many immune responses than IgA, it is therefore important to understand the mechanisms and dynamics of activation of IgG- and IgE-producing B lymphocytes in the non-lymphoid regions of the small intestine.

Helminthic parasites have been observed to augment IgE level in humans and experimental animals, resulting in protective immunity (7-8). But the contribution of IgE to protective immunity in helminthic infections has been fairly elusive, with past research showing no strong evidence as to its role. Recently, however, research has shown direct evidence that IgE (9) as well as IgG (10) are involved in the rapid expulsion of Trichinella spiralis infectious larvae by immune rats. Similar immunity involving IgE has also been found in humans (11) and mice (12, 13). Some recent research further shows evidence of IgE-mediated protective immunity induced by T. spiralis to take place in the epithelial layer of the gut during rapid expulsion (14). Evidence also shows a rapid dissemination of IgE into the intestinal tissue and fluids upon production by B cells, and a delayed appearance of the IgE molecules in the blood circulation (15, 16). These findings support the view that intestinal binding of IgE is not due to parasite-induced local damage or inflammation, but is influenced by IL-4, which stimulates the production of IgE antibodies by B lymphocytes (17). It has been demonstrated that not only did IgE increase during TS infection, concomitant augmentation of IgG was also found in serum (18, 19) and anti-TS IgA was detected in serum and mucus scrapings (20). However, whether intestinal B cells in areas other than the Peyer's patches produce these antibodies has not been studied.

There has been some evidence suggesting IgE-bearing cells seen in the gut of nematode-infected rats to be mast cells due to their expression of receptors specific to the Fc portion of IgE (21). Our study has shown, however, that in the intestine, significant increase in mucosal mast cells takes place at least 9 days after activated T helper cells are transferred (22), indicating that they do not affect the early examination of IgE-bearing B cells. B lymphocyte stimulation by IL-4 and the subsequent production of IgE are known to require genetic differentiation after activation by IL-4 in order to express specific immunoglobulin classes. Yet, this process does not necessarily proceed with a heavy chain switch recombination, thus allowing for the earlier appearance of IgE than was previously thought (23). Recently, it has been shown that eosinophils confer potent antibody-dependent cell-mediated cytotoxicity (ADCC) against TS invasion (17). ADCC is most efficient when the target cell is precoated with antibody, as has been observed in the presence of antibodies against TS newborn larvae (24). TS activated T cells have been identified in the non-Peyer's patch region of the intestine of immunized rats (25) and they have been found to activate B cells in the MLN and the spleen (22).

The purpose of this research was to gain a further understanding of the mechanisms through which T. spiralis activate antibody-producing B lymphocytes in the non-lymphoid regions of the small intestine. It systematically examined the ability of B lymphocytes from the small intestine of immunized rats to express specific antibodies against Trichinella spiralis antigen during an early stage of a primary infection and the host's primary immune response. In addition, the isotypes of specific antibodies produced were identified and the dynamics of appearance of activated B lymphocytes determined. The significance of this study is to reveal the potential ability of an immunized host to generate an early, yet effective, humoral immunity against Trichinella spiralis at the site of non-Peyer's patch region of the small intestine that has been traditionally neglected.