Characterization of B cells in cerebrospinal fluid and peripheral blood in hiv-1 and Cryptococcal meningitis co-infection

Abstract

Introduction: The contribution of B cells to protection against cryptococcal meningitis (CM) is not well defined. To understand the role of B cells to the pathogenesis of CM, we characterized B cell subsets in cerebrospinal fluid (CSF) and peripheral blood (PB) of HIV infected patients with and without CM and compared the findings to healthy adults. Methods: This was a cross sectional study with 48 participants at enrolment. (HIV+CM+); CSF, n=30, PB, n=30, (HIV+CM-); CSF, n=7 & PB, n=1, (HIV-CM-), PB, n=10. Immunophenotyping of B cells was done using flow cytometry. Markers included; CD45, CD19, CD20, CD21, CD38, CD27, IgG and PD-1. Results: Immature transitional B cells (CD20+CD27-IgG-CD38+CD21-), mature transitional (CD19+CD20+CD27-IgG-CD38+CD21+), activated naïve B cells (CD20+CD27-IgG-CD38-CD21-), resting naïve B cells (CD20+CD27-IgG-CD38-CD21+), tissue-like memory (CD20+CD27-IgG+), activated memory (CD20+CD27+CD21-), resting memory (CD20+CD27+CD21+), plasma blasts (CD20-CD27+CD38+CD21-) and exhausted tissue-like memory (CD20-CD27-CD21-) were characterized. Memory B cells predominated CSF in CM, analogous to mature transitional cells in PB mean frequencies (18 % - 56%). Resting naive are however, depleted in CM. CSF B cell phenotypes moderately correlated with PB, (rs=0.4281 to rs=0.6725), (p=0.0091 to p<0.0001). PD-1 was upregulated in CSF mean frequency, (10% to 80%), analogous to (<1% to 40%) in PB. PD-1 inversely correlated with surface IgG (r=-0.3284 to r=-0.6461) and (p=0.0764 to p=0.0002), in CSF or (r= -2085 to r= -0.1715) and (p=3647 to p=0.2690) in PB. Conclusion: B cells heterogeneously traffic and localize into the CSF compartment in HIV and CM co-infection but this phenomenon is down regulated by polarized PD-1 upregulation in CSF B cells. These findings have novel implications in future research involving modalities in CM treatment, prevention and localized CSF/CNS vaccine development. Abstract: 299 words. Key words: Cryptococcal meningitis, Cerebrospinal fluid, peripheral blood, B cells subsets or phenotypes.