The heavy chain immunoglobulin repertoire of human neonatal B cells – human neonatal B cells

The random usage of V, D and J genes and their imprecise recombination, somatic hypermutations, together with the random recombination of heavy and light chains leads to immense antibody diversity. The neonatal immunoglobulin repertoire is significantly different to the adult one, as shown in several studies. But most of these studies focus on the age-related changes in the CDR3 of the heavy chain. The goal of our study was to assess the usage of VH genes in the neonate. By using a single-cell PCR approach with genomic DNA as template we were able to detect both the productively and non-productively rearranged VHDHJH segments. Within the group of productively rearranged VH genes, VH1 was found more often than expected from its presence in the genome, all other families were found as frequently as expected. When the non-productive repertoire was compared to the productive, no significant differences between the VH families were ascertainable. The comparison of the neonatal productive and non-productive repertoires revealed a negative selection of the genes 2–70 and 3–09. There was no positive selection into the productive repertoire observed. In both the non-productive and productive repertoire a very high percentage of neonatal rearrangements used no definable DH genes. The productive rearrangements of neonatal B cells used mainly two JH genes, JH3 and JH4. One third of the non-productive rearrangements used the gene JH4. The comparative analysis between adults and neonates revealed comparable gene usage with only minor differences, suggesting that both repertoires might be generated in response to comparable molecular and selective events as seen for the lambda light chain gene repertoire.

Literatur: H.J. Girschick, A.C. Grammer, T. Nanki, M. Mayo, P.E. Lipsky RAG1 and RAG2 expression in human tonsil and peripheral blood B cells. Journal of Immunology (2001) 166:377-386
H.J. Girschick, P.E. Lipsky The human neonatal Kappa Repertoire, Molecular Immunology (2002) 38:1113-1127.
C. Faber, H. Morbach, S.K. Singh, H.J. Girschick Differential expression patterns of Recombination Activating Genes in individual mature B cells in Juvenile Idiopathic Arthritis Annals of Rheumatic Diseases (2006) 65(10): 1351-1356
P. Richl, U. Stern, P.E. Lipsky, H.J. Girschick The lambda gene immunoglobulin repertoire of human neonatal B cells Molecular Immunology (2008) 45:320-7

development - heavy chain immunoglobulin - human neonatal B cells - immune repertoire - repertoire