Comparison of the frequencies of arginines in heavy chain CDR3 of antibodies expressed in the primary B-cell repertoires of autoimmune-prone and normal mice.
Because the pathogenesis of anti-DNA Ab in SLE is correlated to Ab specificity for native DNA (dsDNA), understanding how such specificity is generated is important. The VH structures of most autoimmune anti-DNA antibodies include at least one arginine in VH-CDR3; moreover, antibody specificity for dsDNA can be correlated to the relative position of arginines in VH-CDR3. The coding sequences for most VH-CDR3 arginines among the anti-DNA MoAbs we have studied to date appeared to have been encoded by sequences generated during V-D-J recombination and would have been expressed in the primary B-cell repertoire. The frequency at which arginine codons are generated during V-D-J recombination therefore could potentially influence the frequency at which DNA-specific B cells are generated in the primary B-cell repertoire. The present study was undertaken to determine whether a higher percentage of B cells in the primary, preautoimmune repertoire of autoimmune-prone (NZB x NZW)F1 mice have immunoglobulin heavy chains with at least one VH-CDR3 arginine compared to B cells in the primary, preimmune repertoire of non-autoimmune-prone BALB/c mice. The present results indicate that mature B cells in preautoimmune (NZB x NZW)F1 mice, whether specific for DNA or not, are no more likely to have heavy chains with VH-CDR3 arginines than are B cells in BALB/c mice. The high frequency of recurrence of VH-CDR3 arginines among autoimmune anti-DNA in (NZB x NZW)F1 mice would appear to derive from the selective oligoclonal expansion of selected B cells that express such structures.
Krishnan
M R
MR
Department of Microbiology and Immunology, The University of Tennessee, Memphis 38163, USA.
Marion
T N
TN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000915:Antibody Affinity; D000917:Antibody Formation / Q000502:physiology; D001120:Arginine / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D002843:Chromatin / Q000276:immunology; D004247:DNA / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D002843:Chromatin; D004277:DNA, Single-Stranded; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D004247:DNA; D001120:Arginine