The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF-and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF-or APRIL-induced Ig secretion because B lymphocytes from TACIknockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF-or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.

Capsular polysaccharides of encapsulated bacteria do not induce immune response in newborns and the mechanism for this unresponsiveness is not clear. In adults, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) is a TNFR family member molecule with a pivotal role in Ab responses against polysaccharide vaccines. We investigated the expression and the functions of the TNF family cytokines, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), and their receptors in newborn mice and found that TACI expression on B lymphocytes was dramatically reduced (p < 0.0001) in newborns as compared with adults. More importantly, TACI ligands BAFF or APRIL were unable to induce IgA/IgG/IgM secretion from newborn B lymphocytes. Additionally, TACI expression seems to be important in plasma cell development. Indeed, in contrast to adults, stimulation of newborn B lymphocytes with BAFF or APRIL did not result in up-regulation of CD138 expression. In vitro or in vivo exposure of newborn B lymphocytes to oligodeoxynucleotides (CpG ODN) led to up-regulation of TACI expression on newly formed, follicular, and marginal zone as well as B1 B lymphocyte populations, and rendered them responsive to BAFF- or APRIL-mediated CD138 expression and IgA/IgG secretion. Finally, immunization of newborn BALB/c mice but not TACI knockout mice with CpG ODN containing (4-hydroxy-3-nitrophenyl)acetyl-Ficoll led to development of IgG Abs against (4-hydroxy-3-nitrophenyl)acetyl. These findings demonstrate that low TACI expression may be a critical factor that determines the susceptibility of newborns to infections with encapsulated bacteria and the impaired immunogenicity of polysaccharide vaccines. Finally, CpG ODNs may correct deficient newborn response to polysaccharide vaccines by up-regulating TACI.

Background: As the number of AIDS cases increases in India, information available among clinicians about the prevalence of opportunistic infections (OIs) is scarce. The aim of the present study was to document the characteristic OIs of HIV-infected North Indian patients along with their CD4 + counts. Patients and Methods:The study group consisted of subjects with confirmed serodiagnosis of HIV, attending the medical clinics at a tertiary health care center in North India. The CD4 + counts were estimated by FACS Calibur (BD) flow cytometer. Simultaneously, routine microbiology smears, cultures and serology were performed to confirm OI. Results: In this retrospective study of 421 subjects, the predominant OI was tuberculosis (47%, 189 cells/µl), followed by parasitic diarrhea (43.5%, 227 cells/µl) and oral candidiasis (25.2%, 189 cells/µl). Conclusion: Tuberculosis was the most frequent OI in the HIV-infected patients studied, and the major mode of transmission of HIV was by sexual route. The median CD4 + counts observed were lower when compared to other studies.

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