The IgG1 B-cell receptor provides survival and proliferative signals analogue to the Igα but not the Igβ co-receptor.

The function of the IgM B-cell receptor (BCR) is dependent on intact signaling of the co-receptors Igα and Igβ, both of which contain a cytoplasmic tail bearing an immunoreceptor tyrosine-based activation motif. We have previously demonstrated that the cytoplasmic tail of the IgG1 BCR can partially compensate for the loss of the signaling moiety of Igα. Here, we show that unlike Igα, Igβ signaling is indispensable for the development and function of IgG1-expressing B cells.

C57BL/6N albino/agouti mutant mice as embryo donors for efficient germline transmission of C57BL/6 ES cells.

We generated C57BL/6NTac mice carrying a tyrosinase loss-of function mutation and a reversion of the nonagouti locus to agouti. This strain has a high superovulation response, allows visual detection of chimeric coat color contribution of C57BL/6 ES-cells and provides a simplified breeding format that generates black G1 offspring of pure inbred C57BL/6 background in one step, providing the ideal host for genetically manipulated C57BL/6 ES cells.

Evaluation of phosphatidylinositol-4-kinase IIIα as a hepatitis C virus drug target.

Phosphatidylinositol-4-kinase IIIα (PI4KIIIα) is an essential host cell factor for hepatitis C virus (HCV) replication. An N-terminally truncated 130-kDa form was used to reconstitute an in vitro biochemical lipid kinase assay that was optimized for small-molecule compound screening and identified potent and specific inhibitors. Cell culture studies with PI4KIIIα inhibitors demonstrated that the kinase activity was essential for HCV RNA replication.

Tracking germinal center B cells expressing germ-line immunoglobulin gamma1 transcripts by conditional gene targeting.

Germinal centers (GCs) represent the main sites for the generation of high-affinity, class-switched antibodies during T cell-dependent antibody responses. To study gene function specifically in GC B cells, we generated Cgamma1-cre mice in which the expression of Cre recombinase is induced by transcription of the Ig gamma1 constant region gene segment (Cgamma1). In these mice, Cre-mediated recombination at the fas, Igbeta, IgH, and Rosa26 loci occurred in GC B cells as early as 4 days after immunization with T cell-dependent antigens and involved >85% of GC B cells at the peak of the GC reaction.

B cell receptor signal strength determines B cell fate.

B cell receptor (BCR)-mediated antigen recognition is thought to regulate B cell differentiation. BCR signal strength may also influence B cell fate decisions. Here, we used the Epstein-Barr virus protein LMP2A as a constitutively active BCR surrogate to study the contribution of BCR signal strength in B cell differentiation.