The story of Bence Jones Proteins
In the last post, we saw the timelines in the discovery of Multiple myeloma.
In this post, we shall see how
Bence Jones protein was discovered.
It was in 1845, in St. George’s Hospital in London, William
MacIntyre, Henry Bence Jones and John Dalrymple examined a
patient of MacIntyre’s who was admitted
with vague uninterrupted pain in the chest, back, and pelvis.
Henry Bence Jones, Picture taken from wikipedia.
MacIntyre asked Henry Bence Jones
to test the patient’s urine. Bence Jones found a substance in the urine that
was precipitated by the addition of nitric acid. He noted that the precipitate
was soluble in boiling water but re-precipitated after the urine was cooled. He
stated the patient had “albumosuria” and
concluded that the protein was an ‘oxide of albumen’ and after subsequent
analysis concluded it was the ‘hydrated deutoxide of albumen’. The patient died soon after the urine was
tested.
John
Dalrymple, was the pathologist
who performed autopsy and noted that the sternum, cervical, thoracic and lumbar
vertebrae were so soft, fragile, and easily breakable that it could be easily
cut with a knife. He also noticed multiple hemorrhagic cavities in bones
throughout the body.
In 1847, a year later, Henry Bence
Jones reported his pre-mortem findings in a short note in the Lancet.
In 1850, MacIntyre summarized
the clinical findings of the case.
The cause of death was given as
“atrophy from albuminuria”. At that time, albuminuria was the term used
nonspecifically to mean proteinuria.
In 1880, Fleischer used the
term “Bence Jones protein” for the first time.
In 1898, Weber postulated
that the bone marrow is the site of production of the Bence Jones protein.
In 1917 and 1921, respectively, Jacobson
and Walters recognized Bence Jones proteins in the bloodstream and
considered that they were probably derived from blood proteins through the
action of abnormal cells in the bone marrow.
In 1922, Bayne-Jones and Wilson
described two groups of Bence Jones protein by immunizing rabbits with
Bence Jones proteins from patients.
In 1956, Korngold from
Memorial Hospital and Rose Lipari, his technician, identified different
classes of Bence Jones proteins. They also demonstrated that antisera to Bence
Jones protein also reacted with the myeloma protein in the blood. As a tribute
to Korngold and Lipari, the two classes of Bence Jones proteins have been
designated kappa and lambda.
In 1958, Harold Porter from
England split the antibody into two major parts, the heavy chains and the light
chains.
In
1962, Gerald M Edelman and Rodney R Porter discovered the chemical structure of
antibodies for which they were awarded Nobel Prize in Medicine or Physiology in
1972.
Gerald M Edelman, Picture from Wikipedia.
Gally looked at the light chains of a patient who had a multiple myeloma with a typical M-spike in the serum. Edelman demonstrated that the light chains in the immunoglobulin molecule in the spike of the monoclonal protein was absolutely identical to the Bence-Jones protein that the patient excreted.
As
Edelman wrote: “Given my hypothesis about myelomas, the thought arose that
perhaps Bence-Jones protein was one of the chains of the myeloma protein that
spilled into the urine because of its relatively low molecular weight (about
22,000)”.
Bence-Jones proteins were simple excreted light chains. Edelman heated a sample of light chain obtained from normal human serum gamma globulins and demonstrated that they had the behavior of Bence-Jones proteins becoming insoluble and then resolubilizing with continued heating.
It took more than 120 years for us
to know the exact nature of Bence Jones proteins.
References:
Domenico Ribatti. A historical perspective on milestones in
multiple myeloma research. Eur J Haematol.2018 Mar;100(3):221-228.
Written
by Dr.Priyavadhana B
Very informative and interesting.
ReplyDeleteThanks Dr.Deepak.
DeleteThank u mam for giving the base of every topic
ReplyDeleteThank you 😊
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