The study investigates the role of bic/microRNA-155 in immune function. Mice deficient in bic/microRNA-155 exhibit immunodeficiency and increased lung airway remodeling, characterized by increased collagen deposition and cell mass of sub-bronchiolar myofibroblasts. These mice show impaired protective immunity, particularly in response to *Salmonella typhimurium* infection and tetanus toxin fragment C protein (TetC) immunization. Bic/microRNA-155 is essential for the function of B and T lymphocytes and dendritic cells (DCs), with defective antigen presentation and costimulatory function in DCs. CD4+ T cells from bic/microRNA-155-deficient mice show altered Th1 and Th2 differentiation, with increased Th2 cytokine production and elevated levels of the transcription factor c-Maf. Microarray analysis identifies a wide spectrum of bic/microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors, suggesting that bic/microRNA-155 plays a key role in immune homeostasis and function. The findings highlight the critical role of bic/microRNA-155 in regulating immune responses and its potential as a therapeutic target for immune-related diseases.The study investigates the role of bic/microRNA-155 in immune function. Mice deficient in bic/microRNA-155 exhibit immunodeficiency and increased lung airway remodeling, characterized by increased collagen deposition and cell mass of sub-bronchiolar myofibroblasts. These mice show impaired protective immunity, particularly in response to *Salmonella typhimurium* infection and tetanus toxin fragment C protein (TetC) immunization. Bic/microRNA-155 is essential for the function of B and T lymphocytes and dendritic cells (DCs), with defective antigen presentation and costimulatory function in DCs. CD4+ T cells from bic/microRNA-155-deficient mice show altered Th1 and Th2 differentiation, with increased Th2 cytokine production and elevated levels of the transcription factor c-Maf. Microarray analysis identifies a wide spectrum of bic/microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors, suggesting that bic/microRNA-155 plays a key role in immune homeostasis and function. The findings highlight the critical role of bic/microRNA-155 in regulating immune responses and its potential as a therapeutic target for immune-related diseases.