B-cell deficiency suppresses vaccine-induced protection against murine filariasis but does not increase the recovery rate for primary infection

Abstract

To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c muMT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil-antibody-B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the muMT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation of L. sigmodontis.

FIG. 1

Polymorphonuclear infiltrated cells in the subcutaneous tissue of mice. (A and B) Intact (A) and degranulated (B) eosinophils, HES staining; (C and D) intact (A) and degranulated (B) eosinophils, MBP immunostaining; (E) neutrophil, HES staining; (F) three intact and two degranulated eosinophils in vaccinated wt mice 6 h p.i., HES staining; (G), intact eosinophils in vaccinated μMT mice 6 h p.i., MBP immunostaining.

FIG. 2

L. sigmodontis recovery rate on day 28 p.i. in μMT and wt mice. vacc, vaccinated; PI, primary-infected. Individual values (n = 6) are presented with the median indicated (bar). ∗, significant difference between the vaccinated wt group and the others.