Journal article
FcRL4 Expression Identifies a Pro-inflammatory B Cell Subset in Viremic HIV-Infected Subjects
Frontiers in immunology, Vol.8, pp.1339-1339
10/20/2017
DOI: 10.3389/fimmu.2017.01339
PMCID: PMC5655023
PMID: 29104574
Abstract
In autoimmune diseases, toll-like receptor (TLR)-stimulated pro-inflammatory IL-6-secreting B cells exert pathogenic roles. Similarly, B cell Fc receptor-like 4 (FcRL4) expression amplifies TLR stimulation, and in rheumatoid arthritis patients, FcRL4 expression identifies a pro-inflammatory B cell subset. B cells from HIV-infected subjects also express heightened levels of FcRL4 and secrete high levels of IL-6: a critical mediator of HIV disease progression. In this study, we sought to determine if FcRL4 identifies a pro-inflammatory B cell subset in HIV-infected subjects and further elucidate the mechanisms underlying FcRL4 amplification of TLR stimulation. We determine that tissue-like memory B cells express the highest endogenous levels of FcRL4 positively correlating with IL-6 expression (p = 0.0022, r = 0.8667), but activated memory B cells exhibit the highest frequency of FcRL4(hi)IL-6(hi) cells. FcRL4(hi) B cells exhibit an activated TLR-signaling pathway identified by elevated phosphorylation levels of: pERK (p = 0.0373), p38 (p = 0.0337), p65 (p = 0.1097), and cJUN (p = 0.0239), concomitant with significantly elevated expression of the TLR-signaling modulator hematopoietic cell kinase (HcK, p = 0.0414). Compared to FcRL4(neg) B cells from healthy controls, TLR9-stimulated FcRL4(pos) B cells express significantly higher levels of lL-6 (p = 0.0179). Further, TLR9-stimulated B cells also upregulate the expression of FcRL4 (p = 0.0415) and HcK (p = 0.0386). In B-cell lines, siRNA-mediated HcK knockdown downmodulates TLR9-induced FcRL4-mediated activation quantified by CD23 upregulation (p = 0.0553). We present data suggesting that, in viremic HIV-infected individuals, FcRL4 expression identifies unique IL-6 producing pro-inflammatory B-cell subsets. Further, TLR stimulation likely modulates FcRL4 expression and FcRL4 expression is associated with Hck, potentially enhancing the activation of TLR-signaling associated transcription factors. Pathogenic B-cells have been identified in other disease settings, and this study represents a novel report describing a pro-inflammatory B cell subset in HIV-infected patients.
Details
- Title: Subtitle
- FcRL4 Expression Identifies a Pro-inflammatory B Cell Subset in Viremic HIV-Infected Subjects
- Creators
- Basile Siewe - Rush University Medical CenterAllison J. Nipper - Rush University Medical CenterHaewon Sohn - National Institute of Allergy and Infectious DiseasesJack T. Stapleton - University of IowaAlan Landay - Rush University Medical Center
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.8, pp.1339-1339
- DOI
- 10.3389/fimmu.2017.01339
- PMID
- 29104574
- PMCID
- PMC5655023
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media Sa
- Number of pages
- 9
- Grant note
- Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; US Department of Veterans Affairs P30 AI-082151-01; P01 AI-076174-01A1 / National Institutes of Health-Developmental Center for AIDS Research RO1 AI-58740 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) I01BX000207 / Veterans Affairs; US Department of Veterans Affairs P30AI082151 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 10/20/2017
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984297425302771
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