The so-called "cold agglutinitis" (CA) are autoreactive antibodies produced
In abnormally large quantities during some autoimmune diseases and other d
isorders, but especially in patients with some Forms of tumors originating
from blood cells, when the production of CA is monoclonal. It is proven tha
t virtually all CA-producing clones in these patients utilize a single gene
segment, V4-34, for the rearrangement of their heavy chain variable region
immunoglobulin genes. Analized literature data as well as results of our o
wn experiments allow us to hypothesize that a significant portion of the no
rmal peripheral blood V4-34-expressing B lymphocytes are in fact autoreacti
ve and may be eliminated from the repertoire by a "timebomb" mechanism that
goes off when the cells are activated via CD40 in peripheral lymphoid orga
ns. An impairment of this "timebomb" mechanism, caused in some autoreactive
, V4-34-expressing clones by oncogenic viruses or some of her unknown facto
rs, may lead to unwanted survival, clonal expansion and, possibly, malignan
t transformation of these clones.