B. APE1 removes deaminated cytosine to create an abasic residue that results in the random insertion of a base during the next round of DNA replication.
C. Frameshift mutations during class switch recombination do not occur because switch regions lie in introns.
D. The error-prone MSH2/6 polymerase repairs DNA lesions and causes mutations that promote somatic hypermutation.
10.11Fill-in-the-Blanks: Fc receptors diversify the effector functions of the distinct antibody isotypes. Most Fc receptors can bind the Fc regions of antibodies with _________ affinity. In contrast, FcεRI binds with ________ affinity. Multivalent antigen-bound IgE can bind _________ in mast cells and cause release of lipid mediators such as _________ and _________. Mast cells also degranulate in response to cross-linking of the FC receptor-bound IgE, which causes release of __________, and as a consequence local blood flow and __________ are increased, initiating an inflammatory response.
General references.
Batista, F.D., and Harwood, N.E.: The who, how and where of antigen presentation to B cells. Nat. Rev. Immunol. 2009, 9:15–27. Nimmerjahn, F., and Ravetch, J.V.: Fcγ receptors as regulators of immune responses. Nat. Rev. Immunol. 2008, 8:34–47. Rajewsky, K.: Clonal selection and learning in the antibody system. Nature 1996, 381:751–758.
Section references.
10-1 Activation of B cells by antigen involves signals from the B-cell receptor and either TFH cells or microbial antigens.
Crotty, S.: T follicular helper cell differentiation, function, and roles in disease. Immunity 2014, 41:529–542.
Maglione, P.J., Simchoni, N., Black, S., Radigan, L., Overbey, J.R., Bagiella, E., Bussel, J.B., Bossuyt, X., Casanova, J.L., Meyts, I., et al.: IRAK-4and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens. Blood 2014, 124:3561–3571.
Pasare, C., and Medzhitov, R.: Control of B-cell responses by Toll-like receptors. Nature 2005, 438:364–368.
Vijayanand, P., Seumois, G., Simpson, L.J., Abdul-Wajid, S., Baumjohann, D., Panduro, M., Huang, X., Interlandi, J., Djuretic, I.M., Brown, D.R., et al.: Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V. Immunity 2012, 36:175–187.
10-2 Linked recognition of antigen by T cells and B cells promotes robust antibody responses.
Barrington, R.A., Zhang, M., Zhong, X., Jonsson, H., Holodick, N., Cherukuri, A., Pierce, S.K., Rothstein, T.L., and Carroll, M.C.: CD21/CD19 coreceptor signaling promotes B cell survival during primary immune responses. J. Immunol. 2005, 175:2859–2867.
Eskola, J., Peltola, H., Takala, A.K., Kayhty, H., Hakulinen, M., Karanko, V., Kela, E., Rekola, P., Ronnberg, P.R., Samuelson, J.S., et al.: Efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy.