The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages of B-cell development

Area of Science:

• Immunology
• Molecular Biology
• Developmental Biology

Background:

• The transcriptional coactivator BOB.1/OBF.1 is essential for B-cell specificity at octamer sites.
• BOB.1/OBF.1 deficiency in mice leads to a lack of germinal center development, indicating a role in antigen-dependent B-cell differentiation.

Purpose of the Study:

• To investigate the role of BOB.1/OBF.1 in earlier stages of B lymphopoiesis.
• To analyze B-cell development in the bone marrow of BOB.1/OBF.1-deficient mice.

Main Methods:

• Analysis of B-cell development in BOB.1/OBF.1-deficient mice.
• Competitive repopulation assays with wild-type and BOB.1/OBF.1(-/-) bone marrow cells.
• Conditional expression of a BOB.1/OBF.1 transgene using a tetracycline-controlled system.

Main Results:

• Reduced numbers of transitional immature B cells (B220(+) IgM(hi)) and increased B-cell apoptosis were observed in BOB.1/OBF.1(-/-) mice.
• BOB.1/OBF.1(-/-) bone marrow cells showed defects in repopulating the B-cell compartment and failed to establish a peripheral presence.
• Conditional BOB.1/OBF.1 expression rescued bone marrow populations but not peripheral IgD(hi) B cells, indicating stage-specific requirements.

Conclusions:

• BOB.1/OBF.1 deficiency causes multistage defects in B-cell development, including impaired transitional B-cell production.
• Defective maturation of recirculating B cells is also a consequence of BOB.1/OBF.1 absence.
• BOB.1/OBF.1 plays critical roles in both early B-cell production and later stages of B-cell maturation.