Somatic hypermutation targeting to intrinsic hotspots of immunoglobulin genes in follicular lymphoma and multiple myeloma

Abstract

In this study, we analyzed the targeting of the somatic hypermutation (SHM) mechanism at specific hotspot sequence motifs in the V H and V genes of 10 follicular lymphoma (FL) cases and the V and V genes of 11 -and six -light chain expressing multiple myeloma (MM) cases. These sequences were analyzed for targeting of specific motifs, ie certain highly mutable trinucleotides (

Characterization of monoclonal anti-β2-glycoprotein-I and anti-prothrombin antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome

“…The multinomial analysis of the distribution of the replacement and silent mutations compared with their respective germ-line genes suggests that those present in Beta 1 and Beta 2 clones are piggy-backed mutations while those of Prot 1 appear to be antigen-driven [23]. This is in line with our findings that most mutational intrinsic hotspots found in Beta 1 and Beta 2 clones are located in framework regions while those present in Prot 1 clustered preferentially in CDRs [24,25]. One previous study utilized the same phage display technology used in our work to generate anti-b 2 GP-I antibodies in scFV format [17].…”

“…We identified the mutational hotspots by the hotspot consensus sequence RGYW, its complementary sequence WRCY (where R ¼ purine, Y ¼ pyrimidine and W ¼A or T) and by the highly mutable trinucleotides (AGC, GCT, ATT, AAT, TAC GTA, AGT and AGA), most of which are part of the RGYW/WRCY motif [24,25].…”

Hla-Do

“…1 It is a mature Bcell lymphoproliferative disorder thought to be derived from germinal center B cells because the neoplastic cells carry ongoing somatic hypermutation in their rearranged immunoglobulin genes and express markers associated with germinal center B cells of secondary follicles. [2][3][4] The distinction between follicular lymphoma and benign follicular hyperplasia often is made based on histologic examination. The demonstration of overexpression of the antiapoptotic protein bcl-2 by immunohistochemical staining or the identification of a monoclonal population of B cells that coexpress CD10 by flow cytometric immunophenotyping helps to confirm the morphologic diagnosis of follicular lymphoma.…”