Epithelial cells of mucosal surfaces are critical for maintaining immune
homeostasis by aiding in the discrimination of pathogenic and commensal
microorganisms and modulating the activities of antigen-presenting
cells and lymphocytes. Functional breakdowns resulting in chronic
infection and inflammation are associated with the development of
hematologic and solid neoplasms for which detailed pathogenetic
mechanisms are poorly understood. Mice heterozygous for a transgene
Col13a1(del) expressing a mutant collagen XIII developed clonal mature
B-cell lineage lymphomas originating in mesenteric lymph nodes (MLN).
The tumors were associated with T cells and macrophages. The incidence
of disease was reduced 2-fold in transgenic mice raised under specific
pathogen-free conditions, suggesting a role for infectious agents. The
lymphomas did not express the mutant collagen XIII, indicating that its
influence on tumorigenesis was B-cell extrinsic and likely to be
associated with collagen XIII-positive tissues drained by the MLN.
Studies of the small intestines of transgenic mice showed that the
subepithelial basement membranes (BM) were highly abnormal and that they
exhibited heightened expression of genes involved in immune responses.
These results define collagen XIII-dependent maintenance of the
intestinal BM as a previously unappreciated component of immune
responses and a critical determinant of cancer susceptibility.