Developmental pathways for B cell lymphogenesis are sufficiently known only in mice and humans. However, both of these species rearrange immunoglobulin heavy chains (IgH) before light chains (IgL) while IgL precedes IgH rearrangement in swine. We demonstrate here that this reversed order of rearrangements have some concealed consequences: (1) we confirmed that although IgLκ rearrangement is initial, most IgLλ+ B cells are generated earlier and before IgH rearrangements, while most IgLκ+ B cells later and after IgH rearrangements, (2) the second IgLκ rearrangement can occur after IgLλ rearrangement, (3) early formed B cells bear only single in-frame IgH rearrangements, (4) many IgLκ+ B cells carry IgLλ rearrangements that can be productive and occurring on both alleles in one cell, and (5) although VpreB and λ5 genes are present in swine, they are preferentially expressed in non-B cells. In summary, our findings reveal that swine use an alternative B cell developmental pathway as compared to mice and humans.

• MeSH
• B-Lymphocytes physiology   MeSH
• Cell Differentiation MeSH
• Gene Rearrangement, B-Lymphocyte MeSH
• Immunoglobulin kappa-Chains genetics   MeSH
• Immunoglobulin lambda-Chains genetics   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mice MeSH
• Swine immunology   MeSH
• Receptors, Antigen, B-Cell genetics   MeSH
• Immunoglobulin Heavy Chains genetics   MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

• MeSH
• Antigens, Neoplasm genetics   MeSH
• Chromosome Deletion * MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell diagnosis   genetics   MeSH
• Genetic Loci * MeSH
• Immunoglobulin lambda-Chains genetics   MeSH
• Immunoglobulin Light Chains genetics   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 22 * MeSH
• Biomarkers, Tumor MeSH
• Repressor Proteins genetics   MeSH
• Comparative Genomic Hybridization MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Research Support, Non-U.S. Gov't MeSH

The technology of array comparative genomic hybridization (array-CGH/aCGH) enabled the identification of novel genomic aberrations in chronic lymphocytic leukemia (CLL) including the monoallelic and biallelic deletions affecting 22q11 locus. In contrast to previous publications, we hypothesized that the described 22q11 deletions are a consequence of the rearrangement of immunoglobulin lambda light chain locus (IGL) segments surrounding several protein-coding genes located in this region. Indeed, using array-CGH and PCR analysis we show that all deletions (n=7) affecting the 22q11 locus in our cohort (n=40) are based on the physiological mechanism of IGL rearrangement. This demonstrates that this loss of genetic material is likely not pathogenic and in fact is merely a marker of IGL rearrangement.

• MeSH
• Antigens, Neoplasm genetics   MeSH
• Chromosome Deletion * MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell genetics   MeSH
• Adult MeSH
• Gene Rearrangement * MeSH
• In Situ Hybridization, Fluorescence MeSH
• Immunoglobulin lambda-Chains genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Chromosomes, Human, Pair 22 genetics   MeSH
• Follow-Up Studies MeSH
• Polymerase Chain Reaction MeSH
• Prognosis MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Comparative Genomic Hybridization MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH