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Variable region gene analysis of pathologic human autoantibodies to the related i and I red blood cell antigens
| Content Provider | Scilit |
|---|---|
| Author | Silberstein, Le Jefferies, Lc Goldman, J. Friedman, D. Moore, Js Nowell, Pc Roelcke, D. Pruzanski, W. Roudier, J. Silverman, Gj |
| Copyright Year | 1991 |
| Description | To investigate the molecular basis of the autoimmune response to the related i and I carbohydrate antigens, we studied cold agglutinins (CA) from B-cell clones and from the peripheral circulation of patients with lymphoproliferative syndromes. Sequence analyses of expressed variable region genes indicate that both anti-i and anti-I specificities from B- cell clones from two patients are encoded by the VH4.21 or a very closely related VH4 heavy chain gene, whereas the expressed light chain genes differed. The anti-i-secreting B-cells express unmutated germline- encoded VH4.21 and VKI gene sequences. The VH region gene encoding anti- I has the closest homology (97%) to the VH4.21 germline gene and differs at the protein level by only three amino acids. In contrast, while the VL region gene encoding anti-I is most homologous (96%) to the VKIII, kv328 germline gene, there are seven amino acid differences due to nonrandom replacement mutations, which suggests a role for antigen-mediated selection in the anti-I response of this individual. These studies were extended by a structural survey of 20 additional serum CA using antipeptide antibodies specific for determinants in VH and VL regions. All anti-I and anti-i CA were shown to express VH4 heavy chains, and 14 of 17 CA expressed a previously described VH4 second hypervariable region determinant, termed VH4-HV2a. We also found that 13 of 14 anti-I CA used VKIII light chains, while the anti-i CA used light chains from at least three VL families. Taken together, the data show that anti-i and anti-I CA probably both derive from the VH4.21 gene (or a closely related gene). Furthermore, the restricted VH and different VL gene use in anti-i and anti-I CA may reflect the close structural relationship of the i and I antigens. |
| Related Links | https://ashpublications.org/blood/article-pdf/78/9/2372/224510/2372.pdf |
| Ending Page | 2386 |
| Page Count | 15 |
| Starting Page | 2372 |
| DOI | 10.1182/blood.v78.9.2372.bloodjournal7892372 |
| Journal | Blood |
| Issue Number | 9 |
| Volume Number | 78 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1991-11-01 |
| Access Restriction | Open |
| Subject Keyword | Medical Laboratory Technology Germline Survey Antigens Closely Related Vh4.21 Vkiii Vh4 Heavy Chains Journal: Blood (Vol- 107, Issue- 9) |
| Content Type | Text |
| Resource Type | Article |
