1. Online Counseling Resource YCMOU ELearning Drive… School of Architecture, Science and Technology Yashwantrao Chavan Maharashtra Open University, Nashik – 422222, India 1

2. © 2008, YCMOU. All Rights Reserved.2 OC-SBT091-CP1-03 Introduction Programmes and Courses  SEP–SBT091–CP1-UN-01 2

3. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.3 Credits  Academic Inputs by Arun Punaji More. M.Sc. (Microbiology) ‏ Experience: 11 Years arunmesh@hotmail.com 3

4. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.4 How to Use This Resource  Counselor at each study center should use this presentation to deliver lecture of 40-60 minutes during Face-To-Face counseling.  Discussion about students difficulties or tutorial with assignments should follow the lecture for about 40-60 minutes.  Handouts (with 6 slides on each A4 size page) of this presentation should be provided to each student.  Each student should discuss on the discussion forum all the terms which could not be understood. This will improve his writing skills and enhance knowledge level about topics, which shall be immensely useful for end exam.  Appear several times, for all the Self-Tests, available for this course.  Student can use handouts for last minutes preparation just before end exam. 4

5. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.5 Learning Objectives  After studying this module, you should be able to: Describe genes encoding for immunoglobulin polypeptides Describe organization of genes encoding for immunoglobulin polypeptides Describe the rearrangement of immunoglobulin genes. 5

6. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.6 Introduction  The immune system has great capability of mounting responses to variety of numerous foreign antigens by producing numerous antibody molecules with diverse specificities.  The immune system accomplish this fate with a limited genes that encode the immunoglobulin molecules.  The immune system have evolved the special mechanisms of producing the antibody with diverse and numerous specificity.  In this module students shall learn about the structures of genes encoding the antibody molecules and the mechanism of production of antibody molecules with diverse and numerous different specificities. 6

7. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.7 Genes Encoding Immunoglobulins-1  Organization of Ig genes:- The development of genes and proteins sequencing technology made it possible to find out the genes encoding for different polypeptide chains of immunoglobulin molecules. It was found that κ, λ light chains and heavy chains are encoded by different families of genes or gene segments situated on different chromosomes. The κ, λ light chains gene families contain three gene segments which are termed as V, J and C gene segments. 7

8. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.8 Genes Encoding Immunoglobulins-2  Organization of Ig genes:-  The heavy chain gene family contain four gene segments which are termed as V, D, J and C gene segments.  During differentiation of B cells, the genes from V and J segments of light chain gene family get rearranged forming a single functional gene called as VJ joint which encode for variable region of light chain.  From the heavy chain gene family, V, D and J gene segments get rearranged forming a single functional gene called as VDJ joint which encode for variable regions of heavy chains. 8

9. School of Science and Technology, Online Counseling Resource… Genes Encoding Immunoglobulins-3 Ig genes encoding for light chain on DNA:- Rearrangement of genes encoding for light chain of antibody 9

10. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.10 Genes Encoding Immunoglobulins-4  Rearrangement of genes encoding for light chains:-  C genes from each of these gene families encode for constant region of heavy chain and light chain.  C genes are arranged sequentially in the order Cμ, Cδ, Cλ, Cε and Cα and expressed in that order only.  The rearranged functional genes for κ, and λ light chains contain following genes from 5' to 3' ends of DNA. C genes for constant region of light chain  Short leader exon sequence  non-coding ( intron) sequence  VJ joint sequence  second intron sequence  C genes for constant region of light chain 10

11. School of Science and Technology, Online Counseling Resource… Gene Encoding for Immunoglobulins-5 Rearrangement of genes encoding for light chains:- – C genes from each of these gene families encode for constant region of heavy chain and light chain. – C genes are arranged sequentially in the order Cμ, Cδ, Cλ, Cε and Cα and expressed in that order only. 11

12. School of Science and Technology, Online Counseling Resource… Gene Encoding for Immunoglobulins-6 Rearrangement of genes encoding for light chains:- – The rearranged functional genes for κ, and λ light chains contain following genes from 5' to 3' ends of DNA. C genes for constant region of light chain Short leader exon sequence non-coding ( intron) sequence VJ joint sequence second intron sequence C genes for constant region of light chain 12

13. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.13 Gene Encoding for Immunoglobulins-7  Rearrangement of light chain genes:-  The two intron sequences between the leader sequence and C gene are removed by RNA processing enzymes from the primary RNA transcript producing mRNA which than exits from the nucleus.  The light chain mRNA thus formed binds to ribosomes and is translated into the light chain polypeptide and its leader sequence is cleaved in the lumen of endoplasmic reticulum. 13

14. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.14 Genes Encoding for Immunoglobulins-8  Rearrangement of heavy chain genes:-  Production of functional genes for heavy chain polypeptide involve two step events.  In the first event DH gene get joined to JH gene forming DH JH joint.  In the second event DH JH joint move toward VH gene and get joined to it forming VHDH JH joint which encode for variable region of heavy chain. The functional gene encoding for complete heavy chain produced after the rearrangement of DNA segments come to possess the following genes starting from the 5' to 3' ends of DNA: 14

15. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.15 Gene Encoding for Immunoglobulins-9  Rearrangement of heavy chain genes:-  Functional genes for heavy chains:-  A short leading L exon sequence  An intron  VDJ joint sequence  second intron  series of C genes segments  once this functional gene segment encoding for heavy chain is produced, RNA polymerase bind to the promoter present upstream from the L exon and transcribe the entire heavy chain genes including introns into primary RNA transcript. 15

16. School of Science and Technology, Online Counseling Resource… Gene Encoding for Immunoglobulins-10  Rearrangement of genes encoding for heavy chain:- 16

17. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.17 What We Learn…..  Genes segments encoding for immunoglobulins.  Organization of immunoglobulins genes.  Rearrangement of immunoglobulin genes. 17

18. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.18 Critical thinking question  Why B cells produce first IgM class of antibody over other classes of antibodies when it come into contact of foreign antigen? 18

19. School of Science and Technology, Online Counseling Resource… © 2008, YCMOU. All Rights Reserved.19 Hints For Critical Thinking Question  sequential expression of heavy chain genes. 19

20. School of Science and Technology, Online Counseling Resource… 20 Study Tips  Book Title: Immunology Title: Immunology Author: Author: Richard A. Goldsby, Thomas Kindt, Barbara A. Osborne. Publication: Publication: W.H. Freeman and Company, New York. Book Title: Title: Microbiology Author: Author: Prescott, Harley and Klein's Publication: Publication: McGraw-Hill international edition. © 2008, YCMOU. All Rights Reserved.

21. 21 End of the Presentation Thank You ! 21