Subepithelial dendritic B cells in orofacial granulomatosis.
BACKGROUND
Orofacial granulomatosis (OFG) is a chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. The pathogenesis is unknown, but it has been linked previously to Crohn's disease (CD) and more recently to dietary sensitivity. The oral mucosa is an immunologically responsive site associated with the generation of protective mucosal and systemic immune responses to vaccination and also hyperresponsiveness to allergens in some individuals. Classically, immune responses in oral mucosa are considered to be mediated by mucosa-associated lymphoid tissues (MALT), secondary lymphoid follicles that are intimately associated with epithelia.


METHODS
Immunohistochemistry was used to investigate the inflammatory infiltrate in OFG and control tissue samples. Polymerase chain reaction (PCR), cloning of PCR products, and sequencing were used to characterize the local immunoglobulin gene profile in OFG.


RESULTS
We describe large, active, dendritic B cells in oral mucosa that were not associated with any organized lymphoid tissues in the local subepithelial microenvironment. They express activation induced cytidine deaminase, which is essential for immunoglobulin gene diversification by somatic hypermutation and class switch recombination. IgE is also expressed by these B cells. They do not align with any other previously described B-cell subset in secondary lymphoid tissues in terms of morphology, proliferative activity, or phenotype.


CONCLUSIONS
These subepithelial dendritic B cells may contribute to the immune responsiveness of the oral mucosa, including IgE-mediated allergic responses. In patients with OFG, further understanding of the role these cells play in oral immunity may lead to novel therapeutic possibilities.
Patel
Pritash
P
Department of Gastroenterology at Guy's & St. Thomas NHS Foundation Trust, London, UK.
Barone
Francesca
F
Nunes
Carlo
C
Boursier
Laurent
L
Odell
Edward
E
Escudier
Michael
M
Challacombe
Stephen
S
Brostoff
Jonathan
J
Spencer
Jo
J
Sanderson
Jeremy
J
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003564:Cytidine Deaminase / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051261:Granulomatosis, Orofacial / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
D007143:Immunoglobulin Heavy Chains; D007073:Immunoglobulin E; D003564:Cytidine Deaminase