Gut-associated lymphoid tissue (GALT) is a microbiota-driven hub of B cell immunity. The gut microbiota maintains GALT in a chronically activated state, supporting the formation and function of germinal centers. This environment influences B cell engagement with antigens and their subsequent responses. GALT differs from other lymphoid tissues in its ability to propagate and select B cells, particularly those recognizing T-cell-independent (TI) antigens. In humans, GALT supports the development of systemic B cells, including innate-like marginal zone B cells that can protect the lungs. GALT is located throughout the gastrointestinal tract and is essential for gut homeostasis and human health. Recent advances highlight the role of GALT in generating antibodies to antigens shared by microbiota species, including TI antigens. Chronic stimulation of GALT B cells creates a niche for B cell maturation and propagation, including marginal zone B cells in humans. GALT is unique in its ability to sample antigens from the gut lumen via the follicle-associated epithelium (FAE), which includes antigen-sampling microfold (M) cells. This process allows for the continuous interaction between immune cells and antigens, leading to ongoing immune responses and the formation of germinal centers. The subepithelial dome (SED) of GALT contains various cell types, including B cells, T cells, and myeloid cells, which contribute to antigen sampling and processing. The unique cellular composition of the SED supports the development of B cells with specific antibody responses. GALT is also involved in the maturation of innate-like marginal zone B (MZB) cells, which are crucial for immune responses to TI antigens. The role of GALT in B cell development and immunity is further supported by studies showing that GALT species, including humans, rely on GALT and microbiota for certain aspects of B cell development. The availability of advanced technologies has enhanced our understanding of GALT's role in immune responses, including the production of IgA antibodies and the selection of high-affinity B cells. Overall, GALT plays a critical role in maintaining gut health and immune responses to pathogens and antigens.Gut-associated lymphoid tissue (GALT) is a microbiota-driven hub of B cell immunity. The gut microbiota maintains GALT in a chronically activated state, supporting the formation and function of germinal centers. This environment influences B cell engagement with antigens and their subsequent responses. GALT differs from other lymphoid tissues in its ability to propagate and select B cells, particularly those recognizing T-cell-independent (TI) antigens. In humans, GALT supports the development of systemic B cells, including innate-like marginal zone B cells that can protect the lungs. GALT is located throughout the gastrointestinal tract and is essential for gut homeostasis and human health. Recent advances highlight the role of GALT in generating antibodies to antigens shared by microbiota species, including TI antigens. Chronic stimulation of GALT B cells creates a niche for B cell maturation and propagation, including marginal zone B cells in humans. GALT is unique in its ability to sample antigens from the gut lumen via the follicle-associated epithelium (FAE), which includes antigen-sampling microfold (M) cells. This process allows for the continuous interaction between immune cells and antigens, leading to ongoing immune responses and the formation of germinal centers. The subepithelial dome (SED) of GALT contains various cell types, including B cells, T cells, and myeloid cells, which contribute to antigen sampling and processing. The unique cellular composition of the SED supports the development of B cells with specific antibody responses. GALT is also involved in the maturation of innate-like marginal zone B (MZB) cells, which are crucial for immune responses to TI antigens. The role of GALT in B cell development and immunity is further supported by studies showing that GALT species, including humans, rely on GALT and microbiota for certain aspects of B cell development. The availability of advanced technologies has enhanced our understanding of GALT's role in immune responses, including the production of IgA antibodies and the selection of high-affinity B cells. Overall, GALT plays a critical role in maintaining gut health and immune responses to pathogens and antigens.