B cells require DOCK8 to elicit and integrate T cell help when antigen is limiting

Area of Science:

• Immunology
• Cell Biology

Background:

• Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome disrupts germinal center (GC) responses.
• GCs are crucial for adaptive immunity, involving B cell proliferation and selection.

Purpose of the Study:

• To elucidate the mechanism by which DOCK8 deficiency impairs B cell maturation.
• To understand the role of antigen availability in B cell-T cell interactions in DOCK8 deficiency.

Main Methods:

• Analysis of DOCK8-deficient B cells in germinal centers of immunized mice.
• Assessment of B cell-T cell interactions, including antigen presentation and costimulation.

Main Results:

• DOCK8-deficient B cells are arrested at a light-zone checkpoint.
• These cells fail to respond to T cell-dependent survival signals, hindering differentiation into plasma or memory B cells.
• Impaired integrin upregulation and conjugate formation limit sustained B cell-T cell activation, especially with limited antigen.

Conclusions:

• DOCK8 deficiency causes a failure in the germinal center response due to impaired B cell selection and survival.
• Limited antigen availability exacerbates B cell-T cell communication defects in DOCK8 deficiency.
• Findings explain humoral response failure in DOCK8 immunodeficiency and highlight antigen's role in immune memory.