Defective B-cell response to T-dependent immunization in lupus-prone mice

Haitao Niu, Eric S. Sobel, Laurence Morel

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Lupus anti-nuclear Ab show the characteristics of Ag-driven T-cell-dependent (TD) humoral responses. If autoAg elicit the same response as exogenous Ag, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone C57BL/6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4- T cells. Multiple defects were found in the B6.TC response to 4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin (NP-KLH) compared with total Ig, including a smaller percentage of B cells participating in the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells (PC) in the bone marrow. B6.TC PC expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident PC prevents the establishment of newly formed NP-specific PC in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous Ag and suggest that low FcγRIIb, hypergammaglobulinemia, and high autoAb production would be predictive of a poor response to immunization in lupus patients.

Original languageEnglish (US)
Pages (from-to)3028-3040
Number of pages13
JournalEuropean Journal of Immunology
Volume38
Issue number11
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Animal models
  • Antibodies
  • Autoimmunity
  • B cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Defective B-cell response to T-dependent immunization in lupus-prone mice'. Together they form a unique fingerprint.

Cite this