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J F Kearney

Publications and source records attributed to J F Kearney.

149 records · Page 9Linked to original sources
PubMedDate not supplied

Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients.

Aberrant regulation of the immune system can lead to the development of autoimmune diseases such as myasthenia gravis. Autoantibodies against the nicotinic acetylcholine receptor (AChR) are found in the serum of myasthenia gravis patients and trigger a reduction of AChR at the muscle endplate resulting in increased muscle fatiguability. It is possible that the autoimmune response results from altered idiotype anti-idiotype network interactions. Here we have used a monoclonal anti-AChR antibody (ACR-24, gamma 1, kappa) in an enzyme-linked immunoabsorbent assay (ELISA) to measure anti-AChR immunoglobulin in human sera. In this assay, ACR-24 is attached to microtitre plates followed by the addition of solubilized human AChR which is bound by the immobilized ACR-24. However, during the development of this assay, it was observed that certain myasthenic patients appeared to have antibodies which bound to ACR-24 alone. This unexpected finding suggested that we had discovered naturally occurring anti-idiotype antibodies in myasthenic sera.

Animals↗
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A biological consequence of variation in the site of D-JH gene rearrangement.

One mechanism which generates diversity in immunoglobulin variable (V) regions is flexibility in the site of recombination among the constituent genetic elements. Within a specific antibody family (that is, a particular VH-VL combination), variability in V-D-J rearrangement not only leads to sequence diversity at the boundary of the juxtaposed genes, but also enables the total length of the third complementarity-determining region (CDR-3) of the heavy chain to be conserved. We demonstrate here that the junctional diversity inherent in rearranged immunoglobulin genes can have consequences for the biology of the immune system. Sequence analysis of the expressed immunoglobulin genes of idiotypically variant as opposed to conventional B lymphocytes of a dominant antibody family showed that the variant B cells undergo a novel D-JH joining event such that an extra amino acid is inserted into the heavy chain CDR-3. The unique D-region conformation possessed by the variant B cells accounts for previous observations which showed that variant and conventional B cells could be differentially regulated in vivo by an autologous set of idiotope-specific B lymphocytes. Our findings indicate that D-region structure can determine the expression of regulatory idiotopes and suggest that the conservation of heavy-chain CDR-3 length within an antibody family may reflect regulatory as well as functional constraints.

Animals↗
PubMedDate not supplied

Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.

The most JH-proximal VH gene segments are used highly preferentially to form VHDJH rearrangements in pre-B-cell lines. This result demonstrates that the rate at which immunoglobulin VH gene segments recombine is influenced by their chromosomal organization, and that the initial repertoire of VH genes expressed in pre-B cells is strikingly different from that seen in mature populations.

Amino Acid Sequence↗