Marginal zone (MZ) B cells, together with other strategically located innate cells, constitute the first line of defense against blood-borne microorganisms, viruses and toxins in the spleen. Their fast and efficient protective antibody responses are well characterized; however, much less is known of their interactions with other cell types during immune responses. Recent work has demonstrated that MZ B cells can directly activate T cells; and MZ B cells also interact with other antigen presenting cells, transporting and concentrating antigen during the course of T-dependent and T-independent immune responses.