title: Monocytoid B cells: an enigmatic B cell subset showing evidence of extrafollicular immunoglobulin gene somatic hypermutation.
abstract: Monocytoid B cells are IgM(+) , IgD(-/+) , CD27(-) B cells, localized in the perisinusoidal area of the lymph node. These cells are especially prominent in infections such as those caused by toxoplasma and HIV. The ontogeny of monocytoid B cells with respect to B cell maturation is incompletely known. We analysed clonal expansion, somatic hypermutation and expression of activation-induced cytidine deaminase (AID) in monocytoid B cells. Sequence analysis of the rearranged immunoglobulin heavy chain genes amplified from microdissected monocytoid B cell zones with a high proportion of proliferating cells reveals the presence of multiple clones with low-level ongoing mutations (mean frequency: 0.46 × 10(-2) per bp). Mutation analysis of these ongoing mutations reveals strand bias, a preference of transitions over transversions as well as the occurrence of small deletions, as observed for somatically mutated immunoglobulin genes in the human germinal centre. Proliferation, ongoing mutation as well as expression of AID, combined, is evidence that monocytoid B cells acquire the mutations in the extrafollicular perisinusoidal area of the lymph node and pleads against a postgerminal centre B cell origin.
authors.affiliation: Department of Pathology, the Norwegian Radiumhospital, University of Oslo, Oslo, Norway. abdirashid.ali.warsame@ous-hf.no
authors.forename: A
authors.initials: A
authors.lastname: Warsame
authors.forename: J
authors.initials: J
authors.lastname: Delabie
authors.forename: A
authors.initials: A
authors.lastname: Malecka
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Trøen
authors.forename: A
authors.initials: A
authors.lastname: Tierens
mesh_terms: D016175:B-Lymphocyte Subsets; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics; D004252:DNA Mutational Analysis; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008198:Lymph Nodes / Q000166:cytology / Q000294:innervation; D009154:Mutation; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007143:Immunoglobulin Heavy Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase