Signal regulatory protein α (SIRPα/CD172a), expressed by myeloid cells including CD11b+ dendritic cells, interacts with ubiquitously expressed CD47 to mediate cell–cell signalling and therefore, may be pivotal in the development of tolerance or immunity. We show that in mice deficient in CD47 (CD47−/−) the cellularity in gut-associated lymphoid tissues is reduced by 50%. In addition, the frequency of CD11b+ CD172a+ dendritic cells is significantly reduced in the gut and mesenteric lymph nodes, but not in Peyer's patches. Activation of ovalbumin (OVA)-specific CD4+ T cells in the mesenteric lymph nodes after feeding OVA is reduced in CD47−/− mice compared with wild-type however, induction of oral tolerance is maintained. The addition of cholera toxin generated normal serum anti-OVA IgG and IgA titres but resulted in reduced intestinal anti-OVA IgA in CD47−/− mice. Replacing the haematopoietic compartment in CD47−/− mice with wild-type cells restored neither the cellularity in gut-associated lymphoid tissues nor the capacity to produce intestinal anti-OVA IgA following immunization. This study demonstrates that CD47 signalling is dispensable for oral tolerance induction, whereas the expression of CD47 by non-haematopoietic cells is required for intestinal IgA B-cell responses. This suggests that differential CD4 T cell functions control tolerance and enterotoxin-induced IgA immunity in the gut.