Th1/Th2 Differentiation and B Cell Function by the Atypical PKCs and Their Regulators

Area of Science:

• Immunology
• Cell Biology
• Molecular Signaling

Background:

• Atypical Protein Kinase Cs (aPKCs), specifically PKCζ and PKCλ/ɩ, and their adapters p62 and Par-6, are key signaling regulators within the PB1-domain-containing group.
• These adapters facilitate the localization of aPKCs into NF-κB and cell polarity pathways, both critical for T cell function.
• The roles of aPKCs and PB1-containing molecules in B and T cell biology, including polarity, survival, and differentiation, are under active investigation.

Purpose of the Study:

• To investigate the role of aPKCs, p62, and Par-4 in controlling B and T cell signaling and differentiation.
• To elucidate the function of PB1-domain-containing signaling regulators in immune cell biology.
• To analyze recent data from gene-knockout (KO) mice to understand in vivo and ex vivo T cell functions.

Main Methods:

• Analysis of gene-knockout (KO) mice deficient in various PB1 molecules.
• Biochemical and genetic evidence gathering.
• Examination of cell polarity control by specific signaling molecules.

Main Results:

• Recent data from KO mice highlight the control of cell polarity by PKCλ/ɩ, PKCζ, p62, and the Par-4 inhibitor in B and T cell signaling and differentiation.
• Evidence points to a PB1-orchestrated signaling network.
• This network is shown to control Th2 differentiation in vitro and in vivo.

Conclusions:

• Genetic and biochemical evidence reveals a PB1-orchestrated signaling network essential for immune cell function.
• This network controls Th2 differentiation in vitro and in vivo.
• It also regulates gene transcriptional programs vital for B cell maturation, function, and Th2 differentiation.