Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis

Ding Chen, Sara J. Ireland, Laurie S. Davis, Xiangmei Kong, Ann M. Stowe, Yue Wang, Wendy I. White, Ronald Herbst, Nancy L. Monson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and longlived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20- plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20- plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20- B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.

Original languageEnglish (US)
Pages (from-to)1541-1549
Number of pages9
JournalJournal of Immunology
Volume196
Issue number4
DOIs
StatePublished - Feb 15 2016

Fingerprint

Autoimmune Experimental Encephalomyelitis
Plasma Cells
Autoantibodies
Multiple Sclerosis
Cerebrospinal Fluid
B-Lymphocytes
Myelin-Oligodendrocyte Glycoprotein
Oligoclonal Bands
Therapeutics
Adaptive Immunity
Bone Marrow
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis. / Chen, Ding; Ireland, Sara J.; Davis, Laurie S.; Kong, Xiangmei; Stowe, Ann M.; Wang, Yue; White, Wendy I.; Herbst, Ronald; Monson, Nancy L.

In: Journal of Immunology, Vol. 196, No. 4, 15.02.2016, p. 1541-1549.

Research output: Contribution to journalArticle

Chen, D, Ireland, SJ, Davis, LS, Kong, X, Stowe, AM, Wang, Y, White, WI, Herbst, R & Monson, NL 2016, 'Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis', Journal of Immunology, vol. 196, no. 4, pp. 1541-1549. https://doi.org/10.4049/jimmunol.1501376
Chen, Ding ; Ireland, Sara J. ; Davis, Laurie S. ; Kong, Xiangmei ; Stowe, Ann M. ; Wang, Yue ; White, Wendy I. ; Herbst, Ronald ; Monson, Nancy L. / Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis. In: Journal of Immunology. 2016 ; Vol. 196, No. 4. pp. 1541-1549.
@article{a2e8a638d8b8424390f2e2afba8bbdbb,
title = "Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis",
abstract = "The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and longlived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20- plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20- plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20- B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.",
author = "Ding Chen and Ireland, {Sara J.} and Davis, {Laurie S.} and Xiangmei Kong and Stowe, {Ann M.} and Yue Wang and White, {Wendy I.} and Ronald Herbst and Monson, {Nancy L.}",
year = "2016",
month = "2",
day = "15",
doi = "10.4049/jimmunol.1501376",
language = "English (US)",
volume = "196",
pages = "1541--1549",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Autoreactive CD19+CD20- plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis

AU - Chen, Ding

AU - Ireland, Sara J.

AU - Davis, Laurie S.

AU - Kong, Xiangmei

AU - Stowe, Ann M.

AU - Wang, Yue

AU - White, Wendy I.

AU - Herbst, Ronald

AU - Monson, Nancy L.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and longlived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20- plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20- plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20- B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.

AB - The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and longlived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20- plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20- plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20- B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.

UR - http://www.scopus.com/inward/record.url?scp=84958549532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958549532&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1501376

DO - 10.4049/jimmunol.1501376

M3 - Article

C2 - 26764035

AN - SCOPUS:84958549532

VL - 196

SP - 1541

EP - 1549

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -