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From rabbit antibody repertoires to rabbit monoclonal antibodies

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ABSTRACT

In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies.

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Ontogeny of rabbit B-cell and antibody repertoires. The three principally different developmental stages of B-cell and antibody diversification in the rabbit are shown. GALT; gut-associated lymphoid tissue; SGC, somatic gene conversion; SHM, somatic hypermutation.
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fig3: Ontogeny of rabbit B-cell and antibody repertoires. The three principally different developmental stages of B-cell and antibody diversification in the rabbit are shown. GALT; gut-associated lymphoid tissue; SGC, somatic gene conversion; SHM, somatic hypermutation.

Mentions: The development of the rabbit B-cell repertoire significantly differs from that of other mammals. The current model proposes a three-step process (Figure 3) consisting of the neonatal B-cell repertoire generated by B lymphopoiesis in the fetal liver and omentum switching to bone marrow after birth, the primary ‘pre-immune' B-cell repertoire evolving during the first 2 months after birth in gut-associated lymphoid tissue (GALT) and the secondary ‘immune' B-cell repertoire generated upon B-cell activation by immunogen binding.2, 67 The neonatal B-cell repertoire starts developing between the second and third week of gestation.68, 69 Interestingly, B lymphopoiesis is very limited in the bone marrow of adult rabbits,70 indicating that B lymphopoiesis is mainly restricted to early development. However, B cells with germline antibody sequences were found in the adult spleen.71 In addition, in a rabbit-to-rabbit adoptive transfer model, it was shown that rabbit B cells were able to engraft into host stem cell niches,72 which led to the conclusion that rabbit B cells are long-lived and potentially self-renewing and may thus sustain the rabbit antibody repertoire throughout a rabbit's lifetime.73


From rabbit antibody repertoires to rabbit monoclonal antibodies
Ontogeny of rabbit B-cell and antibody repertoires. The three principally different developmental stages of B-cell and antibody diversification in the rabbit are shown. GALT; gut-associated lymphoid tissue; SGC, somatic gene conversion; SHM, somatic hypermutation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382564&req=5

fig3: Ontogeny of rabbit B-cell and antibody repertoires. The three principally different developmental stages of B-cell and antibody diversification in the rabbit are shown. GALT; gut-associated lymphoid tissue; SGC, somatic gene conversion; SHM, somatic hypermutation.
Mentions: The development of the rabbit B-cell repertoire significantly differs from that of other mammals. The current model proposes a three-step process (Figure 3) consisting of the neonatal B-cell repertoire generated by B lymphopoiesis in the fetal liver and omentum switching to bone marrow after birth, the primary ‘pre-immune' B-cell repertoire evolving during the first 2 months after birth in gut-associated lymphoid tissue (GALT) and the secondary ‘immune' B-cell repertoire generated upon B-cell activation by immunogen binding.2, 67 The neonatal B-cell repertoire starts developing between the second and third week of gestation.68, 69 Interestingly, B lymphopoiesis is very limited in the bone marrow of adult rabbits,70 indicating that B lymphopoiesis is mainly restricted to early development. However, B cells with germline antibody sequences were found in the adult spleen.71 In addition, in a rabbit-to-rabbit adoptive transfer model, it was shown that rabbit B cells were able to engraft into host stem cell niches,72 which led to the conclusion that rabbit B cells are long-lived and potentially self-renewing and may thus sustain the rabbit antibody repertoire throughout a rabbit's lifetime.73

View Article: PubMed Central - PubMed

ABSTRACT

In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies.

No MeSH data available.


Related in: MedlinePlus