The Xid defect imparts susceptibility to experimental murine filariosis--association with a lack of antibody and IL-10 production by B cells in response to phosphorylcholine.

The pathways conferring immunity to filarial infections are not well known, in part because human pathogenic filariae do not develop a full infection cycle in laboratory mice. Using the permissive infection with Litomosoides sigmodontis in BALB/c mice, we have shown previously that worm development is controlled by CD4+ T cells and is inversely correlated with Th2 cytokine production. Here we analyzed the impact of the Xid immunodeficiency on murine filariosis, comparing the course of infection with L. sigmodontis in BALB/c and B1 cell-deficient BALB.Xid mice. In BALB.Xid mice, 2-3 times more adult worms and up to 10 times more microfilariae compared to BALB/c were observed to develop after infection with infective stage 3 larvae (L3). Parasite-specific Th2 cytokine production by cells from the thoracic cavity, the primary location of the parasites, was diminished significantly in BALB.Xid compared to BALB/c mice. In addition, BALB.Xid mice displayed a significantly lower production of antibodies and B cell-derived IL-10 in response to both L. sigmodontis antigen and phosphorylcholine, a molecule we found to be abundant on the surface of L3. Thus, the B cell-defect in BALB.Xid mice may account for susceptibility to murine filarial infection in two ways, i.e. by the lack of antibody to a dominant surface molecule of invading L3 and by less B cell-derived IL-10 resulting in lower parasite-driven Th2 cytokine production.