Authors: Jamee C. Nixon and Carol F. Webb

Affiliation: Northwest Nazarene University

Title: Deficient Bright Function Leads to an Inefficient Response to Both Phosphorylcholine and to Streptococcus pneumoniae.

Abstract: Bright is a transcription factor that regulates heavy chain production by binding A+T-rich sequences in the intronic enhancer and 5’ flanking region of some variable murine heavy chain promoters.  The 70 kDa protein binds Bruton’s tyrosine kinase (Btk), the defective enzyme in X-linked immunodeficiency, a disease manifested by blocks in B cell development, decreased levels of serum immunoglobulin and increased susceptibility to Streptococcus pneumoniae.  To study Bright’s role in B cell development, a dominant negative (DN) Bright mutant was made that lacked DNA binding activity.  Transgenic mice expressing DN Bright were generated and analyzed for immune deficiencies.  DN Bright mice exhibited decreased serum IgM, poor anti-phosphorylcholine responses and reduced survival rates following Streptococcus pneumonia infection.  These data offer a mechanistic explanation for the abnormal responses to phosphorylcholine and Streptococcus pneumonia observed in Btk-dependent immune deficiencies.