Browse > Article
http://dx.doi.org/10.5483/BMBRep.2019.52.12.232

The Yin and Yang of RNA surveillance in B lymphocytes and antibody-secreting plasma cells  

Lambert, Jean-Marie (UMR CNRS 7276 - INSERM 1268 - Universite de Limoges, Centre de Biologie et de Recherche en Sante)
Srour, Nivine (UMR CNRS 7276 - INSERM 1268 - Universite de Limoges, Centre de Biologie et de Recherche en Sante)
Delpy, Laurent (UMR CNRS 7276 - INSERM 1268 - Universite de Limoges, Centre de Biologie et de Recherche en Sante)
Publication Information
BMB Reports / v.52, no.12, 2019 , pp. 671-678 More about this Journal
Abstract
The random V(D)J recombination process ensures the diversity of the primary immunoglobulin (Ig) repertoire. In two thirds of cases, imprecise recombination between variable (V), diversity (D), and joining (J) segments induces a frameshift in the open reading frame that leads to the appearance of premature termination codons (PTCs). Thus, many B lineage cells harbour biallelic V(D)J-rearrangements of Ig heavy or light chain genes, with a productively-recombined allele encoding the functional Ig chain and a nonproductive allele potentially encoding truncated Ig polypeptides. Since the pattern of Ig gene expression is mostly biallelic, transcription initiated from nonproductive Ig alleles generates considerable amounts of primary transcripts with out-of-frame V(D)J junctions. How RNA surveillance pathways cooperate to control the noise from nonproductive Ig genes will be discussed in this review, focusing on the benefits of nonsense- mediated mRNA decay (NMD) activation during B-cell development and detrimental effects of nonsense-associated altered splicing (NAS) in terminally differentiated plasma cells.
Keywords
Immunoglobulin; Nonsense-associated altered splicing (NAS); Nonsense-mediated mRNA decay (NMD); Plasma cells; RNA surveillance;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Shinkai Y, Rathbun G, Lam KP et al (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855-867   DOI
2 Alt FW and Baltimore D (1982) Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A 79, 4118-4122   DOI
3 Roth DB, Chang XB and Wilson JH (1989) Comparison of filler DNA at immune, nonimmune, and oncogenic rearrangements suggests multiple mechanisms of formation. Mol Cell Biol 9, 3049-3057   DOI
4 Desiderio SV, Yancopoulos GD, Paskind M et al (1984) Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature 311, 752-755   DOI
5 Gilfillan S, Dierich A, Lemeur M, Benoist C and Mathis D (1993) Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science 261, 1175-1178   DOI
6 Kallenbach S, Doyen N, Fanton d'Andon M and Rougeon F (1992) Three lymphoid-specific factors account for all junctional diversity characteristic of somatic assembly of T-cell receptor and immunoglobulin genes. Proc Natl Acad Sci U S A 89, 2799-2803   DOI
7 Komori T, Okada A, Stewart V and Alt FW (1993) Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science 261, 1171-1175   DOI
8 Lafaille JJ, DeCloux A, Bonneville M, Takagaki Y and Tonegawa S (1989) Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell 59, 859-870   DOI
9 Lewis SM (1994) P nucleotide insertions and the resolution of hairpin DNA structures in mammalian cells. Proc Natl Acad Sci U S A 91, 1332-1336   DOI
10 Karousis ED and Muhlemann O (2019) Nonsense-Mediated mRNA Decay Begins Where Translation Ends. Cold Spring Harb Perspect Biol 11, pii: a032862
11 Baumann B, Potash MJ and Kohler G (1985) Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. EMBO J 4, 351-359   DOI
12 Connor A, Wiersma E and Shulman MJ (1994) On the linkage between RNA processing and RNA translatability. J Biol Chem 269, 25178-25184   DOI
13 Jack HM, Berg J and Wabl M (1989) Translation affects immunoglobulin mRNA stability. Eur J Immunol 19, 843-847   DOI
14 Neu-Yilik G, Raimondeau E, Eliseev B et al (2017) Dual function of UPF3B in early and late translation termination. EMBO J 36, 2968-2986   DOI
15 Gudikote JP, Imam JS, Garcia RF and Wilkinson MF (2005) RNA splicing promotes translation and RNA surveillance. Nat Struct Mol Biol 12, 801-809   DOI
16 Eberle AB, Stalder L, Mathys H, Orozco RZ and Muhlemann O (2008) Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region. PLoS Biol 6, e92   DOI
17 Kim YK and Maquat LE (2019) UPFront and center in RNA decay: UPF1 in nonsense-mediated mRNA decay and beyond. RNA N Y N 25, 407-422   DOI
18 Maquat LE (2002) NASty effects on fibrillin pre-mRNA splicing: another case of ESE does it, but proposals for translation-dependent splice site choice live on. Genes Dev 16, 1743-1753   DOI
19 Valentine CR (1998) The association of nonsense codons with exon skipping. Mutat Res 411, 87-117   DOI
20 Nogues G, Kadener S, Cramer P et al (2003) Control of alternative pre-mRNA splicing by RNA Pol II elongation: faster is not always better. IUBMB Life 55, 235-241   DOI
21 Ehlich A, Martin V, Muller W and Rajewsky K (1994) Analysis of the B-cell progenitor compartment at the level of single cells. Curr Biol CB 4, 573-583   DOI
22 McCormack WT, Tjoelker LW, Carlson LM et al (1989) Chicken IgL gene rearrangement involves deletion of a circular episome and addition of single nonrandom nucleotides to both coding segments. Cell 56, 785-791   DOI
23 Outters P, Jaeger S, Zaarour N and Ferrier P (2015) Long-Range Control of V(D)J Recombination & Allelic Exclusion: Modeling Views. Adv Immunol 128, 363-413   DOI
24 ten Boekel E, Melchers F and Rolink A (1995) The status of Ig loci rearrangements in single cells from different stages of B cell development. Int Immunol 7, 1013-1019   DOI
25 Mostoslavsky R, Alt FW and Rajewsky K (2004) The lingering enigma of the allelic exclusion mechanism. Cell 118, 539-544   DOI
26 Gutzeit C, Chen K and Cerutti A (2018) The enigmatic function of IgD: some answers at last. Eur J Immunol 48, 1101-1113   DOI
27 Honjo T, Nagaoka H, Shinkura R and Muramatsu M (2005) AID to overcome the limitations of genomic information. Nat Immunol 6, 655-661   DOI
28 Pilzecker B and Jacobs H (2019) Mutating for Good: DNA Damage Responses During Somatic Hypermutation. Front Immunol 10, 438   DOI
29 Goossens T, Klein U and Kuppers R (1998) Frequent occurrence of deletions and duplications during somatic hypermutation: Implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci U S A 95, 2463-2468   DOI
30 Cenci S and Sitia R (2007) Managing and exploiting stress in the antibody factory. FEBS Lett 581, 3652-3657   DOI
31 Cogne M and Guglielmi P (1993) Exon skipping without splice site mutation accounting for abnormal immunoglobulin chains in nonsecretory human myeloma. Eur J Immunol 23, 1289-1293   DOI
32 Peixeiro I, Inacio A, Barbosa C, Silva AL, Liebhaber SA and Romao L (2012) Interaction of PABPC1 with the translation initiation complex is critical to the NMD resistance of AUG-proximal nonsense mutations. Nucleic Acids Res 40, 1160-1173   DOI
33 Yeap LS, Hwang JK, Du Z et al (2015) Sequence-Intrinsic Mechanisms that Target AID Mutational Outcomes on Antibody Genes. Cell 163, 1124-1137   DOI
34 Cogne M, Bakhshi A, Korsmeyer SJ and Guglielmi P (1988) Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease. J Immunol Baltim Md 1950 141, 1738-1744
35 Cogne M, Silvain C, Khamlichi AA and Preud'homme JL (1992) Structurally abnormal immunoglobulins in human immunoproliferative disorders. Blood 79, 2181-2195   DOI
36 Buhler M, Paillusson A and Muhlemann O (2004) Efficient downregulation of immunoglobulin mu mRNA with premature translation-termination codons requires the 5'-half of the VDJ exon. Nucleic Acids Res 32, 3304-3315   DOI
37 Inacio A, Silva AL, Pinto J et al (2004) Nonsense mutations in close proximity to the initiation codon fail to trigger full nonsense-mediated mRNA decay. J Biol Chem 279, 32170-32180   DOI
38 Buhler M, Mohn F, Stalder L and Muhlemann O (2005) Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes. Mol Cell 18, 307-317   DOI
39 Aoufouchi S, Yelamos J and Milstein C (1996) Nonsense mutations inhibit RNA splicing in a cell-free system: recognition of mutant codon is independent of protein synthesis. Cell 85, 415-422   DOI
40 Buhler M and Muhlemann O (2005) Alternative splicing induced by nonsense mutations in the immunoglobulin mu VDJ exon is independent of truncation of the open reading frame. RNA 11, 139-146   DOI
41 Chemin G, Tinguely A, Sirac C et al (2010) Multiple RNA surveillance mechanisms cooperate to reduce the amount of nonfunctional Ig kappa transcripts. J Immunol Baltim Md 1950 184, 5009-5017
42 Lozano F, Maertzdorf B, Pannell R and Milstein C (1994) Low cytoplasmic mRNA levels of immunoglobulin kappa light chain genes containing nonsense codons correlate with inefficient splicing. EMBO J 13, 4617-4622   DOI
43 Stewart I, Radtke D, Phillips B, McGowan SJ and Bannard O (2018) Germinal Center B Cells Replace Their Antigen Receptors in Dark Zones and Fail Light Zone Entry when Immunoglobulin Gene Mutations are Damaging. Immunity 49, 477-489.e7   DOI
44 Manser T, Tumas-Brundage KM, Casson LP et al (1998) The roles of antibody variable region hypermutation and selection in the development of the memory B-cell compartment. Immunol Rev 162, 183-196   DOI
45 Delpy L, Sirac C, Le Morvan C and Cogne M (2004) Transcription-dependent somatic hypermutation occurs at similar levels on functional and nonfunctional rearranged IgH alleles. J Immunol Baltim Md 1950 173, 1842-1848
46 Allen CD, Okada T and Cyster JG (2007) Germinal-center organization and cellular dynamics. Immunity 27, 190-202   DOI
47 Victora GD and Nussenzweig MC (2012) Germinal centers. Annu Rev Immunol 30, 429-457   DOI
48 Manis JP, Tian M and Alt FW (2002) Mechanism and control of class-switch recombination. Trends Immunol 23, 31-39   DOI
49 Nutt SL, Hodgkin PD, Tarlinton DM and Corcoran LM (2015) The generation of antibody-secreting plasma cells. Nat Rev Immunol 15, 160-171   DOI
50 Todd DJ, McHeyzer-Williams LJ, Kowal C et al (2009) XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development. J Exp Med 206, 2151-2159   DOI
51 Holwerda SJ, van de Werken HJ, Ribeiro de Almeida C et al (2013) Allelic exclusion of the immunoglobulin heavy chain locus is independent of its nuclear localization in mature B cells. Nucleic Acids Res 41, 6905-6916   DOI
52 Mendell JT, ap Rhys CM and Dietz HC (2002) Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science 298, 419-422   DOI
53 Sperling J and Sperling R (2008) Nuclear surveillance of RNA polymerase II transcripts. RNA Biol 5, 220-224   DOI
54 Tinguely A, Chemin G, Peron S et al (2012) Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. Mol Cell Biol 32, 107-117   DOI
55 Takagaki Y, Seipelt RL, Peterson ML and Manley JL (1996) The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell 87, 941-952   DOI
56 Stalder L and Muhlemann O (2007) Transcriptional silencing of nonsense codon-containing immunoglobulin micro genes requires translation of its mRNA. J Biol Chem 282, 16079-16085   DOI
57 Wachtel C, Li B, Sperling J and Sperling R (2004) Stop codon-mediated suppression of splicing is a novel nuclear scanning mechanism not affected by elements of protein synthesis and NMD. RNA 10, 1740-1750   DOI
58 Li S and Wilkinson MF (1998) Nonsense surveillance in lymphocytes? Immunity 8, 135-141   DOI
59 Daly J, Licence S, Nanou A, Morgan G and Martensson IL (2007) Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion. EMBO J 26, 4273-4282   DOI
60 Delpy L, Sirac C, Magnoux E, Duchez S and Cogne M (2004) RNA surveillance down-regulates expression of nonfunctional kappa alleles and detects premature termination within the last kappa exon. Proc Natl Acad Sci U S A 101, 7375-7380   DOI
61 Eberle AB, Herrmann K, Jack HM and Muhlemann O (2009) Equal transcription rates of productively and nonproductively rearranged immunoglobulin mu heavy chain alleles in a pro-B cell line. RNA 15, 1021-1028   DOI
62 Lejeune F (2017) Nonsense-mediated mRNA decay at the crossroads of many cellular pathways. BMB Rep 50, 175-185   DOI
63 Frischmeyer-Guerrerio PA, Montgomery RA, Warren DS et al (2011) Perturbation of thymocyte development in nonsense-mediated decay (NMD)-deficient mice. Proc Natl Acad Sci U S A 108, 10638-10643   DOI
64 Wang J, Hamilton JI, Carter MS, Li S and Wilkinson MF (2002) Alternatively spliced TCR mRNA induced by disruption of reading frame. Science 297, 108-110   DOI
65 Wang J, Chang YF, Hamilton JI and Wilkinson MF (2002) Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay. Mol Cell 10, 951-957   DOI
66 Hwang J and Kim YK (2013) When a ribosome encounters a premature termination codon. BMB Rep 46, 9-16   DOI
67 Weischenfeldt J, Damgaard I, Bryder D et al (2008) NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. Genes Dev 22, 1381-1396   DOI
68 Srour N, Chemin G, Tinguely A et al (2016) A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production. J Exp Med 213, 109-122   DOI
69 Jung D, Giallourakis C, Mostoslavsky R and Alt FW (2006) Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol 24, 541-570   DOI
70 Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S and Papaioannou VE (1992) RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68, 869-877   DOI
71 Chang YF, Imam JS and Wilkinson MF (2007) The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76, 51-74   DOI
72 Lejeune F and Maquat LE (2005) Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr Opin Cell Biol 17, 309-315   DOI
73 Muhlemann O, Mock-Casagrande CS, Wang J et al (2001) Precursor RNAs harboring nonsense codons accumulate near the site of transcription. Mol Cell 8, 33-43   DOI
74 Singh AK, Choudhury SR, De S et al (2019) The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci. ELife 8, pii: e41444
75 Ashi MO, Srour N, Lambert JM et al (2018) Physiological and druggable skipping of immunoglobulin variable exons in plasma cells. Cell Mol Immunol 16, 810-819