DOI Seite / Zitierlink:
https://doi.org/10.11588/diglit.48120#0080
62
Molecular and Cell Biology of Autoantibodies and Autoimmunity
artefacts. Through this work, it has become apparent that both positive selection
for recognition of MHC and negative selection against high affinity anti-self reac-
tivity (clonal abortion) go on within the thymus soon after CD4+ CD8+ T cells
have displayed their T cell receptor molecules. Evidence is mounting that extra-
thymic mechanisms of T cell silencing (clonal anergy) can occur in the periphery
if T cells encounter self antigens in the absence of help.
Tolerance to certain self antigens exists also within the B cell compartement.
For important cell surface antigens, such as self MHC, clonal abortion within the
bone marrow (analogous to thymic self-censorship) occurs. For soluble self an-
tigens, clonal anergy may be induced in immature B cells. This effect has definite
affinity thresholds, and some self antigens fail to induce measurable B cell
tolerance.
Finally, some evidence exists that precursors of memory B cells go through a
“second window” of tolerance susceptibility. Recent work from our laboratory
suggests that in vivo administration of soluble antigen can abrogate the somatic
V gene hypermutation in B cells that underlies affinity maturation. It seems likely
that this mechanism breaks down in autoimmunity, as the pathogenic autoan-
tibodies do display multiple mutations.
Molecular Cloning of a cDNA for the B Polypeptide of the U snRNPs
Y. Ohosone1, T. Mimori2, A. Griffith1, M. Akizuki2, M. Homma2, J. Craft1,
and J. A. Hardin1
'Yale University, New Haven, CT 06510, USA
2Keio University, Tokyo, Japan
Anti-Sm antibodies are a dominant feature of the autoimmune response of
SLE. These antibodies target epitopes found on the B'/B and D polypeptides of
the U series snRNP particles. We have used sera containing this specificity to
isolate and clone cDNAS3~4 (780 bases) which encodes approximately two thirds
of polypeptide B.
To obtain a full length cDNA, we screened a human fibroblast cDNA library
using cDNAs3-4 as a probe and isolated cDNAB (1136 bases). Sequencing dem-
onstrated a single open reading frame encoding a polypeptide of 285 amino acids,
a size closely approximating the B polypeptide. The derived sequence is especially
rich in proline residues and lacks the RNP consensus sequence and the RNA
binding domain common to a number of RNA binding proteins - a finding con-
Molecular and Cell Biology of Autoantibodies and Autoimmunity
artefacts. Through this work, it has become apparent that both positive selection
for recognition of MHC and negative selection against high affinity anti-self reac-
tivity (clonal abortion) go on within the thymus soon after CD4+ CD8+ T cells
have displayed their T cell receptor molecules. Evidence is mounting that extra-
thymic mechanisms of T cell silencing (clonal anergy) can occur in the periphery
if T cells encounter self antigens in the absence of help.
Tolerance to certain self antigens exists also within the B cell compartement.
For important cell surface antigens, such as self MHC, clonal abortion within the
bone marrow (analogous to thymic self-censorship) occurs. For soluble self an-
tigens, clonal anergy may be induced in immature B cells. This effect has definite
affinity thresholds, and some self antigens fail to induce measurable B cell
tolerance.
Finally, some evidence exists that precursors of memory B cells go through a
“second window” of tolerance susceptibility. Recent work from our laboratory
suggests that in vivo administration of soluble antigen can abrogate the somatic
V gene hypermutation in B cells that underlies affinity maturation. It seems likely
that this mechanism breaks down in autoimmunity, as the pathogenic autoan-
tibodies do display multiple mutations.
Molecular Cloning of a cDNA for the B Polypeptide of the U snRNPs
Y. Ohosone1, T. Mimori2, A. Griffith1, M. Akizuki2, M. Homma2, J. Craft1,
and J. A. Hardin1
'Yale University, New Haven, CT 06510, USA
2Keio University, Tokyo, Japan
Anti-Sm antibodies are a dominant feature of the autoimmune response of
SLE. These antibodies target epitopes found on the B'/B and D polypeptides of
the U series snRNP particles. We have used sera containing this specificity to
isolate and clone cDNAS3~4 (780 bases) which encodes approximately two thirds
of polypeptide B.
To obtain a full length cDNA, we screened a human fibroblast cDNA library
using cDNAs3-4 as a probe and isolated cDNAB (1136 bases). Sequencing dem-
onstrated a single open reading frame encoding a polypeptide of 285 amino acids,
a size closely approximating the B polypeptide. The derived sequence is especially
rich in proline residues and lacks the RNP consensus sequence and the RNA
binding domain common to a number of RNA binding proteins - a finding con-