Dual role of the Leishmania major ribosomal protein S3a homologue in regulation of T- and B-cell activation

We have recently characterized a novel Leishmania major gene encoding a pol ypeptide of 30 kDa that was homologous to mammalian ribosomal protein S3a a nd was named LmS3a-related protein (LmS3arp). The protein was found to be e xpressed by all the Leishmania species so far examined (L. infantum, L. ama zonensis, and L. mexicana). In the present study we have extended our appro ach to the analysis of LmS3arp activity on T- and B-cell functions in a mur ine model. The results presented in this report show that LmS3arp plays a d ual role in the regulation of T- and B-cell reactivity. Indeed, we found th at injection of the LmS3arp recombinant protein (rLmS3arp) into BALB/c mice induces preferential activation of B cells, as shown by the following crit eria: (i) increased expression of CD69 molecules on immunoglobulin M (IgM)- secreting spleen cells, (ii) a considerable increase of IgM-secreting B cel ls, and (iii) elevated levels of IgM antibodies in the sera of injected ani mals. Moreover, the IgM antibodies are not specific to the Leishmania antig ens but preferentially recognize heterologous antigens like myosin, thyrogl obulin, DNA, and keyhole limpet hemocyanin. Furthermore, the strong polyclo nal expansion of nonspecific, non-parasite-directed B-cell clones induced b y rLmS3arp is concomitant with a marked inhibition of T-cell proliferation. Analysis of cytokine production revealed a significant downregulation of g amma interferon, interleukin-2 (IL-2), and IL-12 secretion. Taken together, our data suggest that rLmS3arp, through direct or indirect action toward B and T cells and cytokine secretion, could participate in the immunoregulat ory processes that play a role in the balance of the Th1 and Th2 immune res ponse.