Antibody-independent B cell effector functions in relapsing remitting Multiple Sclerosis: Clues to increased inflammatory and reduced regulatory B cell capacity

Sara J. Ireland, Monica Blazek, Christopher T. Harp, Benjamin Greenberg, Elliot M. Frohman, Laurie S. Davis, Nancy L. Monson

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The pathogenic role for B cells in the context of relapsing remitting multiple sclerosis (MS) is incompletely defined. Although classically considered a T cell-mediated disease, B cell-depleting therapies showed efficacy in treating the clinical symptoms of RRMS without decreasing plasma cells or total immunoglobulin (Ig) levels. Here, we discuss the potential implications of antibody-independent B cell effector functions that could contribute to autoimmunity with particular focus on antigen presentation, cytokine secretion, and stimulation of T cell subsets. We highlight differences between memory and naïve B cells from MS patients such as our recent findings of hyper-proliferation from MS memory B cells in response to CD40 engagement. We discuss the implications of IL6 overproduction in contrast to limited IL10 production by B cells from MS patients and comment on the impact of these functions on yet unexplored aspects of B cells in autoimmune disease. Finally, we contextualize B cell effector functions with respect to current immunomodulatory therapies for MS and show that glatiramer acetate (GA) does not directly modulate B cell proliferation or cytokine secretion.

Original languageEnglish (US)
Pages (from-to)400-414
Number of pages15
JournalAutoimmunity
Volume45
Issue number5
DOIs
StatePublished - Aug 2012

Fingerprint

Regulatory B-Lymphocytes
B-Lymphocyte Subsets
Relapsing-Remitting Multiple Sclerosis
B-Lymphocytes
Antibodies
Multiple Sclerosis
Cytokines
Immunomodulation
Antigen Presentation
T-Lymphocyte Subsets
Cell- and Tissue-Based Therapy
Plasma Cells
Autoimmunity
Interleukin-10
Autoimmune Diseases
Immunoglobulins
Interleukin-6
Cell Proliferation
T-Lymphocytes

Keywords

  • B cell APC function
  • B cell co-stimulation molecules
  • B cell cytokines
  • B cell proliferation
  • B-T interaction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Antibody-independent B cell effector functions in relapsing remitting Multiple Sclerosis : Clues to increased inflammatory and reduced regulatory B cell capacity. / Ireland, Sara J.; Blazek, Monica; Harp, Christopher T.; Greenberg, Benjamin; Frohman, Elliot M.; Davis, Laurie S.; Monson, Nancy L.

In: Autoimmunity, Vol. 45, No. 5, 08.2012, p. 400-414.

Research output: Contribution to journalArticle

@article{49f7592581cb43589553dca8dd49a6ac,
title = "Antibody-independent B cell effector functions in relapsing remitting Multiple Sclerosis: Clues to increased inflammatory and reduced regulatory B cell capacity",
abstract = "The pathogenic role for B cells in the context of relapsing remitting multiple sclerosis (MS) is incompletely defined. Although classically considered a T cell-mediated disease, B cell-depleting therapies showed efficacy in treating the clinical symptoms of RRMS without decreasing plasma cells or total immunoglobulin (Ig) levels. Here, we discuss the potential implications of antibody-independent B cell effector functions that could contribute to autoimmunity with particular focus on antigen presentation, cytokine secretion, and stimulation of T cell subsets. We highlight differences between memory and na{\"i}ve B cells from MS patients such as our recent findings of hyper-proliferation from MS memory B cells in response to CD40 engagement. We discuss the implications of IL6 overproduction in contrast to limited IL10 production by B cells from MS patients and comment on the impact of these functions on yet unexplored aspects of B cells in autoimmune disease. Finally, we contextualize B cell effector functions with respect to current immunomodulatory therapies for MS and show that glatiramer acetate (GA) does not directly modulate B cell proliferation or cytokine secretion.",
keywords = "B cell APC function, B cell co-stimulation molecules, B cell cytokines, B cell proliferation, B-T interaction",
author = "Ireland, {Sara J.} and Monica Blazek and Harp, {Christopher T.} and Benjamin Greenberg and Frohman, {Elliot M.} and Davis, {Laurie S.} and Monson, {Nancy L.}",
year = "2012",
month = "8",
doi = "10.3109/08916934.2012.665529",
language = "English (US)",
volume = "45",
pages = "400--414",
journal = "Autoimmunity",
issn = "0891-6934",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Antibody-independent B cell effector functions in relapsing remitting Multiple Sclerosis

T2 - Clues to increased inflammatory and reduced regulatory B cell capacity

AU - Ireland, Sara J.

AU - Blazek, Monica

AU - Harp, Christopher T.

AU - Greenberg, Benjamin

AU - Frohman, Elliot M.

AU - Davis, Laurie S.

AU - Monson, Nancy L.

PY - 2012/8

Y1 - 2012/8

N2 - The pathogenic role for B cells in the context of relapsing remitting multiple sclerosis (MS) is incompletely defined. Although classically considered a T cell-mediated disease, B cell-depleting therapies showed efficacy in treating the clinical symptoms of RRMS without decreasing plasma cells or total immunoglobulin (Ig) levels. Here, we discuss the potential implications of antibody-independent B cell effector functions that could contribute to autoimmunity with particular focus on antigen presentation, cytokine secretion, and stimulation of T cell subsets. We highlight differences between memory and naïve B cells from MS patients such as our recent findings of hyper-proliferation from MS memory B cells in response to CD40 engagement. We discuss the implications of IL6 overproduction in contrast to limited IL10 production by B cells from MS patients and comment on the impact of these functions on yet unexplored aspects of B cells in autoimmune disease. Finally, we contextualize B cell effector functions with respect to current immunomodulatory therapies for MS and show that glatiramer acetate (GA) does not directly modulate B cell proliferation or cytokine secretion.

AB - The pathogenic role for B cells in the context of relapsing remitting multiple sclerosis (MS) is incompletely defined. Although classically considered a T cell-mediated disease, B cell-depleting therapies showed efficacy in treating the clinical symptoms of RRMS without decreasing plasma cells or total immunoglobulin (Ig) levels. Here, we discuss the potential implications of antibody-independent B cell effector functions that could contribute to autoimmunity with particular focus on antigen presentation, cytokine secretion, and stimulation of T cell subsets. We highlight differences between memory and naïve B cells from MS patients such as our recent findings of hyper-proliferation from MS memory B cells in response to CD40 engagement. We discuss the implications of IL6 overproduction in contrast to limited IL10 production by B cells from MS patients and comment on the impact of these functions on yet unexplored aspects of B cells in autoimmune disease. Finally, we contextualize B cell effector functions with respect to current immunomodulatory therapies for MS and show that glatiramer acetate (GA) does not directly modulate B cell proliferation or cytokine secretion.

KW - B cell APC function

KW - B cell co-stimulation molecules

KW - B cell cytokines

KW - B cell proliferation

KW - B-T interaction

UR - http://www.scopus.com/inward/record.url?scp=84863467796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863467796&partnerID=8YFLogxK

U2 - 10.3109/08916934.2012.665529

DO - 10.3109/08916934.2012.665529

M3 - Article

C2 - 22432732

AN - SCOPUS:84863467796

VL - 45

SP - 400

EP - 414

JO - Autoimmunity

JF - Autoimmunity

SN - 0891-6934

IS - 5

ER -