title: Human splenic marginal zone B cells lack expression of activation-induced cytidine deaminase.
abstract: It has been speculated that somatic hypermutation of rearranged immunoglobulin variable (V) region genes does not only take place in the germinal center (GC) microenvironment, but also in the marginal zone (MZ) of the spleen, and that human peripheral blood IgM-positive B cells with somatically mutated V region genes may derive from mutating MZ B cells. As somatic hypermutation is strictly dependent on the enzyme activation-induced cytidine deaminase (AID), we used an AID-specific monoclonal antibody that is suitable for immunohistochemical staining to analyze human splenic MZ cells for AID expression. Analysis of tissue sections from 29 spleens revealed only very rare MZ cells (approx. 0.05%) showing AID staining, whereas in 25 of the spleen samples strong AID staining of GC B cells was observed. Thus, there are virtually no AID-expressing MZ B cells, indicating that somatic hypermutation does not take place at a significant level in the MZ. Consequently, it appears unlikely that the somatically mutated IgM B cells are generated in the splenic MZ. Moreover, the lack of AID-positive MZ B cells questions the recent speculation that B cell chronic lymphocytic leukemias with mutated V genes are derived from mutating MZ B cells.
authors.affiliation: Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt a.M., Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Willenbrock
authors.forename: Berit
authors.initials: B
authors.lastname: Jungnickel
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase