Modulation of Splenic B Cell Subsets during Experimental Leishmania donovani Infection in BALB/c Mice

Abstract

Sodium antimonials are one of the major and common drugs used against visceral form leishmaniasis (VL). However, the development of drug resistance makes it difficult to manage this disease. Current work investigates the modulation of splenic B cells during experimental infection with antimony-sensitive and -resistant Leishmania donovani infection. Here we phenotypically characterized splenic B cell subsets in BALB/c mice infected with antimony drug-sensitive and -resistant VL strains using flow-cytometry method. In the splenocytes we noticed increased number of Transitional T3 B cells and B1a B cells in drug-resistant VL strain infection. Besides, we also observed alteration in Follicular B cell population of antimony-resistant strain infected mice. Drug-resistant strain induced secretion of elevated level of IL-10 from B1a B cells and IL-6 from Transitional T3 B cell subsets in the splenocytes. Purified splenic B cells from antimony drug-resistant strain infected mice showed decrease in the Lyn kinase gene expression compared to sensitive strain infected and uninfected mice. The current study provides insight into changes in host splenic B-cell subsets during experimental infection with antimony-sensitive and -resistant L. donovani in murine model.

Status of B‐Lymphocyte Subsets and Their Homing Markers in Patients With Post‐Kala‐AzarDermal Leishmaniasis

“…In only one study conducted on BALB/c mice infected with L. donovani , an upregulation of CD23 on B cells was reported, and their upregulation was associated with an increased proportion of T2 and T3 transitional B cells [45]. These transitional B cells promote the production of immunosuppressive cytokines IL‐10 and TGF‐β, which favours disease persistence [45]. However, in the context of PKDL, where the levels of TGF‐β and IL‐10 are consistently raised [10], there was a significant decrease in the population of transitional B cells (Figure 2).…”

“…With regard to transitional B cells in human VL and CL, their role and their involvement, if any, in disease progression remain poorly delineated. In only one study conducted on BALB/c mice infected with L. donovani , an upregulation of CD23 on B cells was reported, and their upregulation was associated with an increased proportion of T2 and T3 transitional B cells [45]. These transitional B cells promote the production of immunosuppressive cytokines IL‐10 and TGF‐β, which favours disease persistence [45].…”

Leishmania donovani Exploits Tunneling Nanotubes for Dissemination and Propagation of B Cell Activation

“…Another group of soluble mediators known both to be produced by and to act on B cells is cytokines. Indeed, the production of cytokines such as IL-10, IL-6, and IFN-I by different splenic B cell subsets in response to L. donovani has been demonstrated in multiple studies ( 9 , 10 , 37 ). Despite choosing permeable membrane inserts of a pore size sufficient to allow for the passage of cytokines, as well as vesicles substantially bigger than the average size of shed particles reported in the literature, however, we see no increase in activation in the naive B cells that only are exposed to any soluble mediators but cannot establish direct contact with the parasite, indicating that in the case of B cell activation by L. donovani amastigotes, direct interaction of the parasite with naive B cells is required for their activation.…”