RESUMEN
We have analyzed the sequence of 40 VDJ rearrangements of the immunoglobulin heavy chain gene locus on 32 unselected children from Chile with precursor B cell ALL at diagnosis. Rearrangements were derived by PCR with VH gene family-specific primers and sequenced directly. The number of VDJ rearrangements, and the pattern of VH, DH and JH gene usage was identical to the one reported by groups from developed countries. CDR3 regions represented an unbiased repertoire; VH to JH joinings were in frame in 36% of cases. Absent N nucleotides in the DJ border, suggestive of fetal origin of ALL, were seen in 9/40 rearrangements but they did not correlate with younger age. More than one rearrangement was sequenced in six patients, representing independent events with no signs of clonal evolution. One patient was analyzed at first bone marrow relapse showing persistence of one rearrangement and evolution of a second one which conserved the DJ border. The subset of B cell precursors which suffer malignant transformation to ALL appear to be common in different parts of the world.
Asunto(s)
Reordenamiento Génico de Linfocito B , Genes de Inmunoglobulinas , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Secuencia de Bases , Niño , Preescolar , Chile , ADN Complementario , Femenino , Humanos , Región de Cambio de la Inmunoglobulina/genética , Lactante , Masculino , Datos de Secuencia Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Análisis de Secuencia de ADNRESUMEN
In this report we define ten Salpha1 IGHA1 (*S5-*S14) and nine Salpha2 IGHA2 (*S10-*S18) newly found alleles of the human immunoglobulin switch alpha 1 and switch alpha 2 regions, respectively, in Colombian Indian, Black and Mestizo populations, and a complete list of the SacI and PvuII alleles so far identified as given.
Asunto(s)
Etnicidad/genética , Variación Genética , Región de Cambio de la Inmunoglobulina/genética , Grupos Raciales/genética , Alelos , Población Negra/genética , Colombia , Francia/etnología , Humanos , Indígenas Sudamericanos/genética , Mapeo Restrictivo , Población Blanca/genéticaRESUMEN
We have characterized immunoglobulin switch circular DNA in mice infected with the nematode parasite Nippostrongylus brasiliensis. Two kinds of circular DNA were identified in the lymph nodes as excision products of switch recombination of immunoglobulin heavy-chain constant region (CH) genes. One is a recombinant between C mu and C gamma 1 (gamma 1 circle), and the other is a recombinant between C gamma 1 and C epsilon (epsilon circle). In the epsilon circle, a short piece of switch mu (S mu) sequence was inserted between S epsilon and S gamma 1 sequences. The inserted S mu sequence could be a trace of the preceding switch from C mu to C gamma 1. These findings indicate that parasitic infection can induce class switch recombinations in a successive manner, first from C mu to C gamma 1, and then from C gamma 1 to C epsilon.