Presentation
-
Upload
many87 -
Category
Technology
-
view
162 -
download
0
Transcript of Presentation
![Page 2: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/2.jpg)
![Page 3: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/3.jpg)
B cell activation requires:
• Antigen binding to Ig on cell surface
• CD40/CD40L interaction with activated T cell
• Cytokines produced by activated T cells: IL-4, IL-5, IFN-
• B cell activation leads to: proliferation and differentiation into antibody-producing cells (plasma cells)
![Page 4: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/4.jpg)
![Page 5: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/5.jpg)
![Page 6: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/6.jpg)
![Page 7: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/7.jpg)
Science 281:96, 1998
T and B cells interact in the T cell areas of the LN, activated B cells form a germinal center
![Page 8: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/8.jpg)
Spec. T cells blueB cells brown
T cells brownSpec. B cells blue
Spec T cell brownSpec B cell blue
OVA-HELconjugate
OVA + HEL
![Page 9: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/9.jpg)
![Page 10: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/10.jpg)
![Page 11: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/11.jpg)
![Page 12: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/12.jpg)
Germinal Center Reaction
• Initial contact between B and T cells occurs at the edge of the follicle
• Activated T and B cells migrate into the follicle - initiate germinal center. Only T and B cells recognizing the same antigen are present in GC - clonal populations. Specialized Tfh (follicular helper) subset
• GC develop around a network of follicular dendritic cells (FDC)
• Role of GC: generate memory B cells and potentiate differentiation into high affinity antibody-producing B cells
![Page 13: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/13.jpg)
Immunity 30, March 20, 2009, Fazilleau et al
![Page 14: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/14.jpg)
Annual Reviews
![Page 15: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/15.jpg)
Immunity 29, 2008, Pages 7-9
![Page 16: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/16.jpg)
Nature Immunology 10, 371 - 372 (2009)
![Page 17: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/17.jpg)
![Page 18: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/18.jpg)
Figure 9-7
![Page 19: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/19.jpg)
Figure 9-19
![Page 20: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/20.jpg)
Trends Immunol. 23:31, 2002
![Page 21: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/21.jpg)
![Page 22: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/22.jpg)
QuickTime™ and a decompressor
are needed to see this picture.
(f) Semiquantitative RT-PCR analysis of the expression of AID and IgG1 post-switch transcripts by eGFP+, eGFP+huCD2+ or eGFP-huCD2-CD4+ B cell–T cell conjugates from the draining popliteal lymph nodes of 4get-KN2 mice, sorted 14 d after L. major infection, normalized to Pax5 expression. Results are representative of at least two independent experiments with three serial dilutions (wedges). (g) Section of a draining popliteal lymph node from a KNZ–IFN-gamma reporter mouse 14 d after L. major infection, stained for huCD2 (IL-4 secretion), eYFP (IFN-gamma competence) and PNA (GCs). Original magnification, times 200. Image is representative of at least two independent experiments with six lymph nodes. (h) Semiquantitative RT-PCR analysis of the expression of IgG1 and IgG2a post-switch and germline transcripts and AID by huCD2+CD4+CD19+ (CD2+) or eYFP+ B cell–T cell conjugates (doublets) or eGFP-huCD2-CD4- CD19+ singlets from the draining popliteal lymph nodes of KN2–IFN-gamma mice, sorted 14 d after L. major
infection, normalized to Pax5 expression. Results are representative of at least two independent experiments with three serial dilutions.
QuickTime™ and a decompressor
are needed to see this picture.
![Page 23: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/23.jpg)
Immunity 30, March 20, 2009, Fazilleau et al
![Page 24: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/24.jpg)
Other cytokine effects on B cells
• IL-2: stimulates proliferation• IFN-: Inhibits proliferation
Downregulates MHC expression• IL-4: Stimulates proliferation
upregulates MHC expression• IL-10: Stimulates proliferation
upregulates MHC expressioninduces B cell differentiation
• IL-13: similar effect to IL-4 on human B cells no effect on mouse B cells
![Page 25: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/25.jpg)
Other cytokine effects on B cells
• TGF-: inhibits proliferation• IL-17: induces germinal center formation Maintains GCmay play a role in auto-antibody
production• IL-6: Induces B cell proliferationinduces B cell differentiation
increase IgG production
![Page 26: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/26.jpg)
Co-stimulatory molecules are required for GC formation:CD40/CD40L, CD28 and ICOSMembers of the TNF family are also required
![Page 27: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/27.jpg)
Immunol. Rev. 156:127, 1997
![Page 28: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/28.jpg)
![Page 29: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/29.jpg)
B cells in the GC
• Proliferate in dark zone - centroblasts
• Undergo somatic hypermutation during this phase
• Positive selection for high affinity - centrocyte:FDC interaction
• Negative selection for autoreactive B cells - B:T cell interaction
![Page 30: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/30.jpg)
CDR1, 2, 3 of Ab molecule contact antigen
![Page 31: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/31.jpg)
Open square: early primaryClosed square: late primaryDiamond: secondaryTriangle: tertiary
Affinity of Ab increases witheach immunization and so does the number of mutations
Fundamental Immunology TextbookEditor W.E. Paul
![Page 32: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/32.jpg)
Mutations are clustered in the CDRs and contribute to the increase in affinity.
Fundamental Immunology TextbookEditor W.E. Paul
![Page 33: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/33.jpg)
Location of cells in GC determined by chemokinesCXCL13 in light zone attracts CXCR5+ T and B cellsCXCL12 in dark zone attracts CXCR4+ B cells
![Page 34: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/34.jpg)
![Page 35: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/35.jpg)
Figure 9-15
![Page 36: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/36.jpg)
Trends Immunol. 22:361, 2001
![Page 37: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/37.jpg)
Immunity 30, March 20, 2009, Fazilleau et al
![Page 38: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/38.jpg)
![Page 39: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/39.jpg)
![Page 40: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/40.jpg)
![Page 41: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/41.jpg)
![Page 42: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/42.jpg)
![Page 43: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/43.jpg)
Figure 9-10
![Page 44: Presentation](https://reader033.fdocuments.net/reader033/viewer/2022060119/558c8f15d8b42a10268b4664/html5/thumbnails/44.jpg)