IRTA1+ monocytoid B cells in reactive lymphadenitis show a unique topographic distribution and immunophenotype and a peculiar usage and mutational pattern ofIgVH genes

• DOI: 10.1002/path.1944
• Publication Date: 2006-02-28T16:46:47Z
• Authors: S Lazzi; C Bellan; E Tiacci; N Palummo; R Vatti; M Oggioni; T Amato; K Schuerfeld; T Tonini; P Tosi; B Falini; L Leoncini
• Keywords: 0301 basic medicine; 572; Immunoglobulin Heavy Chain; 2734; DNA Mutational Analysis; B-Lymphocyte Subsets; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Immunoglobulin Variable Region; Receptors, Cell Surface; Antigen selection; 612; Receptors, Fc; Polymerase Chain Reaction; Immunology; Maturation of B cells; lymphadenitis; Immunophenotyping; DNA Mutational Analysi; Toxoplasmosi; 03 medical and health sciences; Lymphadenitis; Receptors; Immunoglobulin; Humans; Antigens; CD27; B-Lymphocyte Subset; Gene Rearrangement; Superantigen; Superantigens; Fc; Genes, Immunoglobulin; B-Lymphocyte; IRTA1; Germinal Center; Antigen selection; CD27; IRTA1; Monocytoid B cells; Toxoplasmic lymphadenitis; Antigens, CD27; B-Lymphocyte Subsets; DNA Mutational Analysis; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Germinal Center; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Immunophenotyping; Lymphadenitis; Microdissection; Polymerase Chain Reaction; Receptors, Cell Surface; Receptors, Fc; Superantigens; Toxoplasmosis; Genes, Immunoglobulin; 2734; Tumor Necrosis Factor Receptor Superfamily, Member 7; Toxoplasmic lymphadeniti; Genes; Cell Surface; Heavy Chain; Monocytoid B cell; Immunoglobulin Heavy Chains; Microdissection; Toxoplasmosis; Human; Lymphadeniti

The origin and function of monocytoid B cells (MBCs) are poorly understood. Taking advantage of their strong expression of IRTA1 (a receptor that is also associated with MALT marginal zone B cells), we have comprehensively analysed MBCs in 25 cases of lymphadenitis of different aetiologies, shedding new light on the topographical distribution, immunophenotype and IgV(H) gene usage and mutational profile of this B cell subset. IRTA1(+) MBCs, although predominantly located in the subcapsular and intermediary sinuses, were also observed scattered within germinal centres (GCs) in all lymphadenitis cases examined. The molecular characterization of IgV(H) genes revealed that IRTA1(+) MBCs residing in different areas of the lymph node (subcapsular sinus, intermediary sinuses and GCs) can be clonally related (with intraclonal variation), and that those located in GCs are consistently more mutated and selected for expression of a functional antigen receptor than those located in the sinuses. Moreover, by contrast, IRTA1(+) MBCs in GCs express the memory B cell marker CD27. Finally, in toxoplasmic lymphadenitis, the IRTA1(+) MBC population shows a highly preferential usage of the V(H) genes 3-7 and 3-30 (without any obvious peculiarity in their CDR3s), possibly suggesting that a superantigen expressed by Toxoplasma gondii may be involved in the early activation of this B cell subset.