Abstract:
:X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease in man, characterized by an arrest in B lymphocyte differentiation at the precursor B cell stage. The structure of expressed immunoglobulin (Ig) kappa light (L) chain rearrangements of nine B lymphoblastoid cell lines from one XLA patient was investigated by amplification of cDNA by the polymerase chain reaction using 5' V kappa family-specific primers and a 3' kappa constant region primer. Members of all four V kappa gene families were found to be utilized in Ig kappa L chain rearrangements at frequencies that were consistent with random V kappa family usage. There was no preference for usage of any particular kappa joining segment. Additional diversity was generated by deletions and random nucleotide insertions at the site of juxtaposition. Particular V kappa members seemed to be overrepresented in the sample. The observed homology of the V kappa I, V kappa II and V kappa III region sequences, both to each other and to known germ-line V kappa sequence indicated the absence of somatic mutations in the majority of these expressed Ig genes. In contrast of the single-member V kappa IV family four different sequences were found to be expressed. That these sequences were mutated derivatives of a germ-line V kappa IV element was substantiated both by sequence analysis and oligonucleotide hybridization. This finding shows that the mutation process can occur in early stages of B cell development i.e. before H chain class switch has occurred. The presence of these mutations is probably independent of clonal expansion since XLA patients are unable to respond to antigen. We conclude that the differentiation arrest in XLA does not preclude early onset of somatic mutation events in V kappa gene segments.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Timmers E,Hermans MM,Kraakman ME,Hendriks RW,Schuurman RKdoi
10.1002/eji.1830230306subject
Has Abstractpub_date
1993-03-01 00:00:00pages
619-24issue
3eissn
0014-2980issn
1521-4141journal_volume
23pub_type
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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