Immune Netw.  2003 Jun;3(2):89-95. 10.4110/in.2003.3.2.89.

N-Region Addition in Immunoglobulin Kappa Light Chains in B Cell Subsets in Rheumatoid Arthritis: Evidence for Over-expression of TDT in B Lineage

• Lee CW
• Bridges SL

• KMID: 2150573
• DOI: http://doi.org/10.4110/in.2003.3.2.89

Abstract

BACKGROUND
Unusually high amounts of N region addition and CDR3 length diversity were found in immunoglobulin (Ig) light chain Vk and Jk joins in patients with rheumatoid arthritis (RA). We sought to determine whether this finding is due to excessive activity of the enzyme responsible for N region addition (terminal deoxynucleotidyl transferase [TdT]) in B lineage cells in bone marrow or from positive antigenic selection of B cells with long CDR3 lengths. METHODS: We used FACS to isolate IgM+ /IgD+ B cells (predominantly naive) and IgM- IgD- B cells (predominantly class-switched) B cells from peripheral blood of a patient with RA known to have enrichment for long Vk CDR3s and from that of two normal controls. RT-PCR of VkIII transcripts was performed, followed by sequencing of individual cDNA clones. We analyzed the CDR3 lengths and N region additions in 97 clones. RESULTS: There was enrichment for long CDR3 lengths (11 or 12 amino acids) in both IgM+ /IgD+ and IgM- IgD- B cells in RA compared to B cell subsets in the normal controls. The IgM+/IgD+ B cell subset in RA was markedly enriched for N region addition and was similar to that seen in the IgM-/IgD- subset. CONCLUSION: These data suggest that enrichment for N region addition and long CDR3 lengths in RA may result from unusually high or prolonged activity of TdT in bone marrow.

Keyword

Rheumatoid arthritis; N region; CDR3

MeSH Terms

Arthritis, Rheumatoid*
B-Lymphocyte Subsets*
B-Lymphocytes
Bone Marrow
Clone Cells
DNA Nucleotidylexotransferase
DNA, Complementary
Humans
Immunoglobulins*
DNA Nucleotidylexotransferase
DNA, Complementary
Immunoglobulins