Here, to investigate the intrinsic role of B cell-TLR9 in obesity, we generate C57BL/6 (B6) mice with B cell-specific deficiency of Tlr9 (Tlr9fl/fl/Cd19Cre+/- B6) and use a high fat diet-induced obesity (HFDIO) model system to study the effect of B cell-specific deficiency of Tlr9 on local and systemic immunity and the effect on gut microbiota. The gene discussed is TLR9; the disease is obesity disorder.