A point mutation in the Cstyle value="smcaps">h3 domain of human IgG3 inhibits antibody secretion without affecting antigen specificity
- 作者：McLean ; Gary R. ; Torres ; Marcela ; Trotter ; Brendon ; Noseda ; Michela ; Bryson ; Steve ; Pai ; Emil F. ; et. al.
- 关键词：Recombinant immunoglobulin ; Chimeric IgG3 ; Secretion defect ; Cryptococcus neoformans ; Punctate immunofluorescence
- 刊名：Molecular Immunology
- 出版年：2005
- 期刊代码：112_01615890
- 类别：bio
- 出版时间：May, 2005
- 卷：42
- 期：9
- 页码：1111-1119
- 文件大小：358 K
摘要
Immunoglobulins (Ig) require correct folding and assembly of both heavy (H) and light (L) chains to form a functional H<sub>2sub>L<sub>2sub> dimer that is secreted from plasma cells. This process is dependent upon the endoplasmic reticulum (ER) chaperone BiP, which targets improperly, folded or assembled Ig molecules for degradation. While investigating the mechanism of low IgG3 secretion, we identified a missense mutation L368P in the C<span class="smCaps">hspan>3 region of the human γ3 H-chain that was associated with impaired secretion of intact and functional Ig. The non-secreted H-chains displayed slower electrophoretic migration than secreted H-chains, consistent with them being glycosylated in the ER but not fully processed in the golgi apparatus and secretory pathway. Reversion of the mutated codon to wild type restored secretion of the IgG3, which displayed the same fine specificity for antigen as non-secreted IgG3. However, the non-secreted IgG3 was not opsonic in an in vitro phagocytosis assay. The results indicate that correct IgG3 C<span class="smCaps">hspan>3 domain folding is essential for secretion and effective function but does not affect specificity for antigen.