DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE

 

PUBLIC HEALTH SERVICE . BETHESDA 14, MD.

 

NATIONAL INSTITUTES OF HEALTH

OLiver 6-4000 March 28, 1960

Dr. Joshua Lederberg
Stanford University Medical School
Stanford, California

Dear Doctor Lederberg:

In the process of preparing a manuscript which describes the
results of some experiments on anti sheep erythrocyte hemolysin formation in
C3H mice bearing transmissible plasma cell tumors (X5563) I would like to
ask your opinion upon applicability to these results of the elective theory
of antibody formation which you recently published in Science (129: 1649, 1959).

Following a single immunizing injection of sheep erythrocytes to mice
bearing these tumors one observes significantly reduced circulating hemolysin
titers in some mice or the complete lack of demonstrable amounts of the anti-
body. A second injection of the antigen after an interval of 7 to 21 days
results in a secondary response which agrees very favorably with the response
seen in the non tumor bearing mice serving as controls.

It would seem possible to explain this result within the framework
presented in your discussion referred to above. If one assumes that the
actively growing neoplasm invades and perhaps destroys some of the rela-
tively small number of antibody producing cells participating in the primary
response then the observed reduction in titer would follow. To explain the
absence of demonstrable circulating hemolysin in about 0% of the tumor mice
(singly immunized) it is necessary to conclude that the circulating antibody
was present in amounts below the sensitivity of the titration procedure.
Since none of the mice stimulated with a second antigen injection failed to
produce circulating hemolysin in very satisfactory amounts it would seem
that at least a few clones "genotypically adapted" must have been produced
by the first antigen stimulation.

Since this tumor (X5568) resembles human multiple myeloma in some
respects it is possible that some metabolic disturbance might explain the
observed results. I would appreciate any comment you would care to make
relative to the attempt to explain the observations briefly described above.

Sincerely yours,
aa leeucer Jue \

Falconer Smith, Head
Radiation Biology Section
Radiation Branch

National Cancer Institute

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