1. History of Immunology Core Module Immunology
Doctoral Training Group GK1660
Erlangen  2011
History of Immunology
Comments – Mitchell & Miller, JEM II. 1968i
(Receptor Editing)
Hans-Martin Jäck
Division of Molecular Immunology
Dept. Of Internal Medicine III
Nikolaus-Fiebiger-Center
University of Erlangen-Nürnberg

2. The Journal of Experimental Medicine 128: 821-37 (1968)
Jaques Miller
Born 1931 Nice
Australia

3. What was know about the involvement of cells in tiggering antbody responses
Pre 1968

4. Mice

5. Miller 1961
Thymus is required for
transplant rejection

6. Antibody-secreting cells can easily be visualized by plaques
Jerne Plaque Assay 1963
Science (1963), p. 405
Antibody-secreting cells can easily be visualized by plaques

7. Thymus cells are required for producing antibody secreting cells
Miller 1965: Thmyus and antibodies
Thymus cells are required for producing antibody secreting cells

8. Chicken

9. Bursa cells are required for producing antibody secreting cells
Click 1955: Bursa and antibodies
J. Poultry Sci.
Bursa cells are required for producing antibody secreting cells

10. Cooper & Good (1965) chicken
Bursa are required and thymus are important for effciceint antibody production

11. Mice

12. Claman (1966)
Bone marrow and thymus cells are required for formation of antibody-secreting cells

13. Do antibody-secreting cells come from the thymus or the bone marrow?
The big question:
Do antibody-secreting cells come from the thymus or the bone marrow?

14. The Journal of Experimental Medicine 128: 821-37 (1968)
Jaques Miller
Born 1931 Nice
Australia

15. Experimental Set-Up
Restored of hematopetic system by transplanting bone marrow cells into lethally irradiated mice
ATxBM mice (for Adult Thymectomized, Bone-Marrow estored).
Bone marrow can have different marker than thymus cells
Immunological equivalent to neonatally tymectomized mice
Used anti-H2 antibodies to distinguish between thymus- and bone marrow- derived cells
Transer pf thymus and TDL (thoracic duct lymphocytes)
TDL are lymphocyte precursors of immune effector cells (Gowan1958)
TDL more potent in restoring IR than thymus cells

16. B- and T Lymphocytes (Roitt 1969)
The first mentionning
of the the terms
B lymphocytes
and T lymphocytes
????

17. TDLs complete function of thymus
TDLs restore efficiently formation of
antibody-secreting cells

18. Bone marrow cells develop into ASC
Hypothesis. ASC originate form bone marrow cells
Strain H2
ATxBM Host CBA H-2d
BM CBA H-2d
TDL (F1) Bl6 x CBA H-2b/d

19. Bone marrow cells develop into ASC
Hypothesis. ASC originate form bone marrow cells

20. Conclusion - Miller 1968 “While both bone-marrow thymus-derived)
Cells are required to generate a humoral response to SRBC, only the bone marrow-derived cells develop into
antibody-forming cells, while the T-cells perform a "helper" function”

21. How do T cells help B cells to develop into antibody-secreting cells??
What next?
How do T cells help B cells to develop into
antibody-secreting cells??

22. Brief Sidevisit
- MHC Haplotype -

23. Peptid in Bindungsspalte
MHC Molecules
MHC I
MHC II
Peptidbindungs
spalte
Peptid in Bindungsspalte
Janeway

24. MHC Locus - Mouse Polygen mehrere Gene für eine MHC-Kette
Polymorph mehrere Formen eines Gens (Allels)
Beispiele für Nomenklatur:
Mensch:
HLA-B15, Allel 15 des Klasse I B-Gens
Maus:
H-2Kb, b-Allel des Klasse I K-Gens
I-Ak, k-Allel des Klasse II A-Gens
Koordinierte Expression
(alle Gene werden exprimiert)
Ko-dominante Expression
(beide Allele werden exprimiert)

25. MHC Locus - Mouse

26. MHC Haplotypes (Set of alleles) Part 1

27. MHC Haplotypes (Set of alleles) Part 2

28. Ig Loci in mice H locus k locus l locus ca. 2.5 Mb (mouse) stem cell
V segments
D segments
J segments C
stem cell
k locus
V segments
J segments Ck
Kappa deleting elements
l locus
Gerdes and Wabl, 2002

29. Radiation Chimeras
“an experimentally produced animal containing hemopoeitic cells of a genotype different from that of the rest of the organism”
→ has the immunologic characteristics of both host and donor

30. Does BCR has to reach the surface torecognize self-antigen
Problems:
Gene was deleted in ALL cells (genomic KO). Effect on e.g. Ab production could come from B cells or other cells
Does BCR has to reach the surface torecognize self-antigen
Bone marrow
Fetal liver
Recipent
Donor
Recipients receives a single dose of radiation that kills the stem cells of the bone marrow and much of the differentiated hemopoeitic tissue.
Recipient receives bone marrow or fetal liver cells from nonirradiated donors.
The injected stem cells home to the recipient's bone marrow sites and begin repopulating them, and ultimately they replace the recipient's hemopoeitic tissues.