Gene-conversion in rabbit B-cell ontogeny and during immune responses in splenic germinal centers

Mage, Rose G.; Sehgal, Devinder; Schiaffella, Enrico

doi:10.1016/s0165-2427(99)00110-5

Cited by 11 publications

(13 citation statements)

References 34 publications

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“…More recently, the importance of GALT as a site for diversification of the rearranged genes that encode Ab H chains was demonstrated (11,14,15). The present study considerably extends these earlier observations by presenting an extensive analysis of sequence diversification during the development of rabbit appendix follicles and GCs between 3 and 9 wk after birth.…”

Section: Gene Conversion Occurs In Both Rearranged H and L Chain Genesupporting

confidence: 70%

“…5) and the HCDR3 sequences of members of large clones from anti-DNP splenic GCs collected on day 15 (5). The marked contrast between the sequences from cells in expanding Ag-specific clones from spleens and those from young appendix suggests that the latter are developing a diverse set of combining sites consistent with their proposed role as a source of the rabbit's preimmune repertoire (13,14,18).…”

Section: Extensive Diversification In the Cdr3 During Clonal Expansiomentioning

confidence: 85%

“…1 and Refs. [12][13][14][15]. These cells are the hypothesized source of the primary repertoire, i.e., B cell precursors generated to exit to the periphery and respond to specific Ags (14).…”

Section: Gene Conversion Occurs In Both Rearranged H and L Chain Genementioning

confidence: 99%

“…Just as bursectomy leads to deficiencies in numbers of chicken B cells and their repertoire of specificities, neonatal appendectomy and removal of other GALT early in life leads to B cell deficiency (10) and diminished diversity of V H D H J H gene sequences in B cells of young rabbits (11). Remarkable development and expansion of B cells takes place in rabbit appendix between birth and 6 wk of age (10,(12)(13)(14). It is accompanied by diversification of rearranged V H D H J H sequences (14,15) and dependent upon the presence of normal gut flora (16 -18).…”

mentioning

confidence: 99%

“…Remarkable development and expansion of B cells takes place in rabbit appendix between birth and 6 wk of age (10,(12)(13)(14). It is accompanied by diversification of rearranged V H D H J H sequences (14,15) and dependent upon the presence of normal gut flora (16 -18).…”

mentioning

confidence: 99%

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Distinct Clonal Ig Diversification Patterns in Young Appendix Compared to Antigen-Specific Splenic Clones

Sehgal

Obiakor

Mage

2002

The Journal of Immunology

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The young rabbit appendix is a dynamic site for primary B cell repertoire development. To study diversification patterns during clonal expansion, we collected single appendix B cells from 3- to 9-wk-old rabbits and sequenced rearranged H and L chain genes. Single cells obtained by hydraulic micromanipulation or laser capture microdissection were lysed, PCR amplified, and products directly sequenced. Gene conversion-like changes occurred in rearranged H and L chain sequences by 3–4 wk of age. Somatic mutations were found in the D regions that lack known conversion donors and probably also occurred in the V genes. A few small sets of clonally related appendix B cells were found at 3–5 wk; by 5.5 wk, some larger clones were recovered. The diversification patterns in the clones from appendix were strikingly different from those found previously in splenic germinal centers where an immunizing Ag was driving the expansion and selection process toward high affinity. Clonally related appendix B cells developed different amino acid sequences in each complementarity-determining region (CDR) including CDR3, whereas dominant clones from spleen underwent few changes in CDR3. The variety of combining sites generated by diversification within individual clones suggests that at least some clonal expansion and selection, known to require normal gut flora, may be driven through indirect effects of microbial components rather than solely by their recognition as specific foreign Ags. This diversity of combining sites within B cell clones supports the proposed role of appendix in generating the preimmune repertoire.

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Section: Gene Conversion Occurs In Both Rearranged H and L Chain Genesupporting

confidence: 70%

Section: Extensive Diversification In the Cdr3 During Clonal Expansiomentioning

confidence: 85%

Section: Gene Conversion Occurs In Both Rearranged H and L Chain Genementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Distinct Clonal Ig Diversification Patterns in Young Appendix Compared to Antigen-Specific Splenic Clones

Sehgal

Obiakor

Mage

2002

The Journal of Immunology

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Opinions on the Nature of B-1 Cells and Their Relationship to B Cell Neoplasia

Potter¹,

Melchers²

2000

Current Topics in Microbiology and Immunology

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Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives

Parray

Shukla

Samal

et al. 2020

International Immunopharmacology

147

125

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The advancements in technology and manufacturing processes have allowed the development of new derivatives, biosimilar or advanced improved versions for approved antibodies each year for treatment regimen. There are more than 700 antibody-based molecules that are in different stages of phase I/II/ III clinical trials targeting new unique targets. To date, approximately more than 80 monoclonal antibodies (mAbs) have been approved. A total of 7 novel antibody therapeutics had been granted the first approval either in the United States or European Union in the year 2019, representing approximately 20% of the total number of approved drugs. Most of these licenced mAbs or their derivatives are either of hybridoma origin or their improvised engineered versions. Even with the recent development of high throughput mAb generation technologies, hybridoma is the most favoured method due to its indigenous nature to preserve natural cognate antibody pairing information and preserves innate functions of immune cells. The recent advent of antibody engineering technology has superseded the species level barriers and has shown success in isolation of hybridoma across phylogenetically distinct species. This has led to the isolation of monoclonal antibodies against human targets that are conserved and non-immunogenic in the rodent. In this review, we have discussed in detail about hybridoma technology, its expansion towards different animal species, the importance of antibodies isolated from different animal sources that are useful in biological applications, advantages, and limitations. This review also summarizes the challenges and recent progress associated with hybridoma development, and how it has been overcome in these years to provide new insights for the isolation of mAbs.

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Gene-conversion in rabbit B-cell ontogeny and during immune responses in splenic germinal centers

Cited by 11 publications

References 34 publications

Distinct Clonal Ig Diversification Patterns in Young Appendix Compared to Antigen-Specific Splenic Clones

Distinct Clonal Ig Diversification Patterns in Young Appendix Compared to Antigen-Specific Splenic Clones

Opinions on the Nature of B-1 Cells and Their Relationship to B Cell Neoplasia

Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives

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