VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis

Gregory P. Owens, Kimberly Winges, Alanna M. Ritchie, Sydni Edwards, Mark P. Burgoon, Laura Lehnhoff, Kirsten Nielsen, John Corboy, Donald H. Gilden, Jeffrey L. Bennett

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138+ plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138+ cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138+ cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138+ cells with functionally rearranged VH4 gene segments as an overriding feature of MS CeSF repertoires. VH4 dominance was attributed to the preferential selection of specific VH4 genes, particularly gene segment VH4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in VH4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)6343-6351
Number of pages9
JournalJournal of Immunology
Volume179
Issue number9
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Humoral Immunity
Multiple Sclerosis
Cerebrospinal Fluid
Genes
Immunoglobulin G
B-Lymphocytes
Oligoclonal Bands
Plasma Cells
Blood Cells
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology

Cite this

Owens, G. P., Winges, K., Ritchie, A. M., Edwards, S., Burgoon, M. P., Lehnhoff, L., ... Bennett, J. L. (2007). VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis. Journal of Immunology, 179(9), 6343-6351.

VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis. / Owens, Gregory P.; Winges, Kimberly; Ritchie, Alanna M.; Edwards, Sydni; Burgoon, Mark P.; Lehnhoff, Laura; Nielsen, Kirsten; Corboy, John; Gilden, Donald H.; Bennett, Jeffrey L.

In: Journal of Immunology, Vol. 179, No. 9, 01.11.2007, p. 6343-6351.

Research output: Contribution to journalArticle

Owens, GP, Winges, K, Ritchie, AM, Edwards, S, Burgoon, MP, Lehnhoff, L, Nielsen, K, Corboy, J, Gilden, DH & Bennett, JL 2007, 'VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis', Journal of Immunology, vol. 179, no. 9, pp. 6343-6351.
Owens GP, Winges K, Ritchie AM, Edwards S, Burgoon MP, Lehnhoff L et al. VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis. Journal of Immunology. 2007 Nov 1;179(9):6343-6351.
Owens, Gregory P. ; Winges, Kimberly ; Ritchie, Alanna M. ; Edwards, Sydni ; Burgoon, Mark P. ; Lehnhoff, Laura ; Nielsen, Kirsten ; Corboy, John ; Gilden, Donald H. ; Bennett, Jeffrey L. / VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis. In: Journal of Immunology. 2007 ; Vol. 179, No. 9. pp. 6343-6351.
@article{42719feaf22249979419957c20e94aa8,
title = "VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis",
abstract = "A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138+ plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138+ cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138+ cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138+ cells with functionally rearranged VH4 gene segments as an overriding feature of MS CeSF repertoires. VH4 dominance was attributed to the preferential selection of specific VH4 genes, particularly gene segment VH4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in VH4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.",
author = "Owens, {Gregory P.} and Kimberly Winges and Ritchie, {Alanna M.} and Sydni Edwards and Burgoon, {Mark P.} and Laura Lehnhoff and Kirsten Nielsen and John Corboy and Gilden, {Donald H.} and Bennett, {Jeffrey L.}",
year = "2007",
month = "11",
day = "1",
language = "English (US)",
volume = "179",
pages = "6343--6351",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - VH4 gene segments dominate the intrathecal humoral immune response in multiple sclerosis

AU - Owens, Gregory P.

AU - Winges, Kimberly

AU - Ritchie, Alanna M.

AU - Edwards, Sydni

AU - Burgoon, Mark P.

AU - Lehnhoff, Laura

AU - Nielsen, Kirsten

AU - Corboy, John

AU - Gilden, Donald H.

AU - Bennett, Jeffrey L.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138+ plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138+ cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138+ cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138+ cells with functionally rearranged VH4 gene segments as an overriding feature of MS CeSF repertoires. VH4 dominance was attributed to the preferential selection of specific VH4 genes, particularly gene segment VH4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in VH4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.

AB - A characteristic feature of the CNS inflammatory response in multiple sclerosis (MS) is the intrathecal synthesis of IgG and the presence of oligoclonal bands. A strong correlation between CD138+ plasma blast numbers in MS cerebrospinal fluid (CeSF) and intrathecal IgG synthesis suggests that these cells are the major Ab-secreting cell type in MS CeSF. Sequencing of V regions from CD138+ cells in MS CeSF has revealed somatically mutated and expanded IgG clonotypes consistent with an Ag-targeted response. In the present study, single-cell RT-PCR analysis of CD138+ cells from 11 MS patients representing differing clinical courses and stages of disease identified expansion of CD138+ cells with functionally rearranged VH4 gene segments as an overriding feature of MS CeSF repertoires. VH4 dominance was attributed to the preferential selection of specific VH4 genes, particularly gene segment VH4-39, which displayed a significant enrichment in CeSF compared with MS peripheral blood B cells. A modest increase in VH4 prevalence among MS peripheral blood IgG memory cells was also noted, suggesting that factors shaping the CD138 repertoire in CeSF might also influence the peripheral IgG memory cell pool. These results indicate a highly restricted B cell response in MS. Identifying the targets of CeSF plasma cells may yield insights into disease pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=36749072673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36749072673&partnerID=8YFLogxK

M3 - Article

C2 - 17947712

AN - SCOPUS:36749072673

VL - 179

SP - 6343

EP - 6351

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -