leprae, T

cells and B cells to the relatively increased IgM observed in L-lep lesions. The expression of IL-5 and B-cell markers and of functional genes in L-lep lesions is consistent with the overall T helper type 2 cytokine pattern in L-lep lesions compared with T-lep lesions,3 as well as the elevated systemic humoral response that is prominent in L-lep patients.13,14 The polar L-lep and T-lep clinical presentations correlate with the level of cell-mediated immunity against M. leprae, as well as the cytokine patterns in the skin lesions, with Th2 cytokines (IL-4, IL-5 and IL-10) expressed in L-lep lesions and Th1 cytokines (IL-2 JAK inhibitor and IFN-γ) in T-lep lesions [2–4]. In fact, type 2 cytokines such as IL-4 and IL-10 have negative immunoregulatory roles in the context of infection [5, 6], and antibody responses are greater in lepromatous patients, suggesting that humoral immunity is not protective. Linking the gene expression data at the site of disease,3,10 our in vitro data suggest that the effects of IL-5 on increased IgM secretion from B cells requires the presence of T cells, because only PBMC, but not purified B cells, resulted in increased IgM in response to IL-5 (Fig. 7).

Although several in vitro studies have shown that IL-5 enhances IgA production by activated B cells either alone or with transforming growth factor-β, we did not observe any statistically significant enhancement of IgA production in cultures supplemented with IL-5.15–18 However, TGF-b1 Akt inhibitor gene expression is increased in L-lep versus T-lep lesions (fold change 1.9, P < 0.005), which may provide a mechanism for the comparatively increased IgA detected in the L-lep lesions. In addition, Mizoguchi et al.19 showed that IL-5 can elicit the maturation of CD40-activated B cells to

IgM-secreting cells in LPS-activated B cells. Lastly, Bertolini et al. showed that IL-5 can augment Staphylococcal A Cowan I strain-stimulated purified human B lymphocytes to produce IgM, but not IgA or IgG, and our result suggesting a T-cell requirement is consistent with their finding that IL-5 effects are enhanced in co-operation with IL-2.20,21 The presence of B cells in leprosy tissue was initially Non-specific serine/threonine protein kinase described by Ridley.22 Subsequently, B cells were identified by the expression of CD20 (cell surface marker for immature and mature circulating B cells), CD79 (associates with the B-cell receptor complex), and CD138 (cell surface marker for plasma cells) in active lesions from L-lep patients.23 Consistent with our gene expression data, we found that B cells, and specifically plasma cells, are expressed at the site of infection in leprosy and are 15% more abundant in L-lep lesions than in T-lep lesions. We were able to demonstrate by immunolabelling that surface IgM and IgA were consistently expressed within L-lep lesions.