Specific over-expression of deltex and a new Kelch-like protein in human germinal center B cells.
Ig gene hypermutation was originally described as the molecular process underlying B cell affinity maturation following a T-dependent immune response. Somatic hypermutation is also used in some species such as sheep, to generate diversity during formation of the primary antibody repertoire. In sheep, B cells mutate their Ig receptor during antigen-independent development in the lymphoid follicles of ileal Peyer's patches, but this process is arrested when these same B cells are cultured in vitro. We have used these differences between in vivo and in vitro B cell development to perform a cDNA subtraction between these two cell populations, in order to search for genes that might be involved in the hypermutation process. We describe in this paper the characterization of two genes, highly expressed in sheep ileal Peyer's patch B cells and also in centroblasts of human tonsils: deltex (Drosophila) homolog 1 (DTX1), which is related to the Notch pathway and a new Kelch-like protein, KLHL6. The putative role of these proteins, which are more likely involved in the germinal center B cell differentiation pathway than in the hypermutation mechanism per se, is discussed.
Gupta-Rossi
Neetu
N
INSERM U373, Faculté de Médecine Necker-Enfants Malades, 156 Rue de Vaugirard, 75730 Paris Cedex 15, France.
Storck
Sebastien
S
Griebel
Philip J
PJ
Reynaud
Claude-Agnès
CA
Weill
Jean-Claude
JC
Dahan
Auriel
A
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D027041:Somatic Hypermutation, Immunoglobulin; D014018:Tissue Distribution
D002352:Carrier Proteins; D018076:DNA, Complementary; C473356:KLHL6 protein, human; C489839:Klhl6 protein, mouse; D011506:Proteins; C409218:deltex protein, vertebrate