Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion

Viraj P. Ichhaporia, Tyler Sanford, Jenny Howes, Tony Marion, Linda M. Hendershot

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Sil1 is a nucleotide exchange factor for the endoplasmic reticulum chaperone BiP, and mutations in this gene lead to Marinesco-Sjögren syndrome (MSS), a debilitating autosomal recessive disease characterized by multisystem defects. A mouse model for MSS was previously produced by disrupting Sil1 using gene-trap methodology. The resulting Sil1Gt mouse phenocopies several pathologies associated with MSS, although its ability to assemble and secrete antibodies, the best-characterized substrate of BiP, has not been investigated. In vivo antigen-specific immunizations and ex vivo LPS stimulation of splenic B cells revealed that the Sil1Gt mouse was indistinguishable from wild-type age-matched controls in terms of both the kinetics and magnitude of antigen-specific antibody responses. There was no significant accumulation of BiP-associated Ig assembly intermediates or evidence that another molecular chaperone system was used for antibody production in the LPS-stimulated splenic B cells from Sil1Gt mice. ER chaperones were expressed at the same level in Sil1WT and Sil1Gt mice, indicating that there was no evident compensation for the disruption of Sil1. Finally, these results were confirmed and extended in three human EBV-transformed lymphoblastoid cell lines from individuals with MSS, leading us to conclude that the BiP cofactor Sil1 is dispensable for antibody production.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalMolecular Biology of the Cell
Volume26
Issue number3
DOIs
StatePublished - Feb 1 2015

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Nucleotides
Antibodies
Antibody Formation
B-Lymphocytes
Antigens
Transformed Cell Line
Molecular Chaperones
Human Herpesvirus 4
Endoplasmic Reticulum
Genes
Immunization
Pathology
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion. / Ichhaporia, Viraj P.; Sanford, Tyler; Howes, Jenny; Marion, Tony; Hendershot, Linda M.

In: Molecular Biology of the Cell, Vol. 26, No. 3, 01.02.2015, p. 420-429.

Research output: Contribution to journalArticle

Ichhaporia, Viraj P. ; Sanford, Tyler ; Howes, Jenny ; Marion, Tony ; Hendershot, Linda M. / Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion. In: Molecular Biology of the Cell. 2015 ; Vol. 26, No. 3. pp. 420-429.
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