B cells from patients with multiple sclerosis have a pathogenic phenotype and increased LTα and TGFβ1 response
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B cells from patients with multiple sclerosis have a pathogenic phenotype and increased LTα and TGFβ1 response. / McWilliam, Oskar; Sellebjerg, Finn; Marquart, Hanne V.; von Essen, Marina Rode.
I: Journal of Neuroimmunology, Bind 324, 2018, s. 157-164.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - B cells from patients with multiple sclerosis have a pathogenic phenotype and increased LTα and TGFβ1 response
AU - McWilliam, Oskar
AU - Sellebjerg, Finn
AU - Marquart, Hanne V.
AU - von Essen, Marina Rode
PY - 2018
Y1 - 2018
N2 - The contribution of B cells to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is currently of great interest due to the positive outcomes of treatment with B cell-depleting monoclonal antibodies. In this exploratory study we examined the phenotype and cytokine response of B cells from untreated patients with RRMS and healthy controls. The CNS migration potential of the individual blood B cell subpopulations was evaluated according to the expression of CD49d, ALCAM, CXCR3, and CCR7, and cerebrospinal fluid (CSF) samples were analyzed to establish the phenotype of migrated B cells. The frequency of the individual blood B cell subsets expressing CD5, CD43, CD69, CD80, CD83, DC-SIGN and CD138 was similar in patients with RRMS and healthy controls. However, a higher percentage of CD27-IgD-IgM+ memory B cells were found in the blood of patients with RRMS, a population also identified in the CSF samples. We also observed an increased percentage of B cells producing LTα and a higher level of TGFβ1 in patients with RRMS. Altogether, we found that patients with RRMS have an increased frequency of blood CD27-IgD-IgM+ memory B cells that are recruited to the CSF together with other memory B cell populations. Furthermore, we report an increased B cell production of LTα and TGFβ1 in patients with RRMS.
AB - The contribution of B cells to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is currently of great interest due to the positive outcomes of treatment with B cell-depleting monoclonal antibodies. In this exploratory study we examined the phenotype and cytokine response of B cells from untreated patients with RRMS and healthy controls. The CNS migration potential of the individual blood B cell subpopulations was evaluated according to the expression of CD49d, ALCAM, CXCR3, and CCR7, and cerebrospinal fluid (CSF) samples were analyzed to establish the phenotype of migrated B cells. The frequency of the individual blood B cell subsets expressing CD5, CD43, CD69, CD80, CD83, DC-SIGN and CD138 was similar in patients with RRMS and healthy controls. However, a higher percentage of CD27-IgD-IgM+ memory B cells were found in the blood of patients with RRMS, a population also identified in the CSF samples. We also observed an increased percentage of B cells producing LTα and a higher level of TGFβ1 in patients with RRMS. Altogether, we found that patients with RRMS have an increased frequency of blood CD27-IgD-IgM+ memory B cells that are recruited to the CSF together with other memory B cell populations. Furthermore, we report an increased B cell production of LTα and TGFβ1 in patients with RRMS.
U2 - 10.1016/j.jneuroim.2018.09.001
DO - 10.1016/j.jneuroim.2018.09.001
M3 - Journal article
C2 - 30244922
VL - 324
SP - 157
EP - 164
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
ER -
ID: 217340780