Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 1, Pages 476-484Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.1.476
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Funding
- NCI NIH HHS [P30CA68485] Funding Source: Medline
- NHLBI NIH HHS [P01HL68744] Funding Source: Medline
- NIAID NIH HHS [AI060729-01, F32-AI069770-01] Funding Source: Medline
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Prefoldin is a hexameric chaperone that facilitates posttranslational folding of actins and other cytoskeletal proteins by the Tcp1-containing ring complex chaperonin, TriC. The present study characterized mice with a null mutation in Pfdn1, which encodes the first subunit of the Prefoldin complex. Pfdn1-deficient mice displayed phenotypes characteristic of defects in cytoskeletal function, including manifestations of ciliary dyskinesia, neuronal loss, and defects in B and T cell development and function. B and T cell maturation was markedly impaired at relatively early stages, namely at the transitions from pre-pro-B to pre-B cells in the bone marrow and from CD4(-)CD8(-) double-negative to CD4(+)CD8(+) double-positive T cells in the thymus. In addition, mature B and T lymphocytes displayed cell activation defects upon Ag receptor cross-linking accompanied by impaired Ag receptor capping in B cells. These phenotypes illustrate the importance of cytoskeletal function in immune cell development and activation.
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