Rabbit Appendix Research Articles

Comportamiento productivo y aspecto histológico del intestino delgado y apéndice cecal de conejos alimentados con triticale adicionando xilanasa

The objective was to evaluate the addition of xylanase on the productive performance and histological aspects of the small intestine and cecal appendix of rabbits fed diets containing triticale. 120 rabbits were randomly distributed to one of the four treatments differentiating them from the inclusion of xylanase (0, 4000, 8000 y 12000 XU/kg, respectively), the animals were weighed weekly and at the end of the experimental period, the rabbits were slaughtered taking samples of the duodenum, jejunum and cecal appendix to perform the technique of staining with Hematoxylin-Eosin (HE). An analysis of variance was performed using the GLM procedure of SAS (2002) and Tukey’s test. The addition of xylanase enzyme increased (p<0.05) the live weight at day 4 and 7 of the rabbits and increased (p<0.05) the areas of intestinal villi of the duodenum, jejunum and cecal appendix.

Ultrasound morphology of cecal appendix in pet rabbits.

Cecal appendix is the terminal part of cecum and is characteristic of rabbit, among domestic animals. The purpose of this work is to evaluate its morphology upon ultrasound. A prospective study was planned for the duration of approximately 1year. Rabbits presented in the study period for abdominal ultrasound with no clinically evident alterations of the gastrointestinal tract were eligible for inclusion in the study. Abdominal ultrasound was performed under manual restrain with a high frequency linear probe (8-18MHz). Cecal appendix was visualized in 40/42 rabbits (95.2%) with median or left paramedian views. The wall appeared multilayered in accordance with normal bowel anatomy, and the luminal content showed in all cases an alimentary pattern. Measurement of appendix wall thickness (AWT) was possible in all 40 rabbits in which the appendix was visualized while measurement of the appendix diameter (AD) was possible in 39 rabbits. Reference intervals for AWT were 1.1-2.1mm, and for AD were 3.9-8.8mm. There was a negative correlation between age and AWT (r = -0.35, P = 0.027) and a moderate positive correlation between AWT and AD (r = 0.71, P < 0.001). Cecal appendix is recognizable via ultrasound in the vast majority of rabbits. We describe the normal morphological aspect of the appendix and we provide reference intervals for wall thickness and diameter of the appendix, in order to aid in the diagnosis of disorders of the appendix. The negative correlation between age and AWT indicates lower values of AWT associated with increasing age that could represent the physiological decrease in the immunitary function of the appendix in aged rabbits.

Immunomorphologic transformation of the appendix of rabbits after antigenic loading using anti-pneumococcal prophylactic preparation «Pneumo-Pro»

Despite a widespread introduction of immunoprophylaxis, the national scientific literature doesn’t frequently deal with the data containing a detailed description of the morphological state of the immune system’s central and peripheral organs, as well as their immunomorphological rearrangement after the use of vaccines and the effects of immunostimulants. It is also worth noting that such organ of the peripheral immune system as a vermiform appendix was mainly ignored by the domestic scientists. The vermiform appendix is a lymphoepithelial organ that performs a protective function and relates to the peripheral part of the immune system. The development, proliferation and differentiation of immunocompetent cells occurs inside this important formation, first and foremost, of B-cell subpopulations. Vermiform appendix is sometimes called the tonsils of the abdominal cavity due to the high concentration of lymphoid cells in it. We did not find a detailed description of the morphological changes of the rabbits’ vermiform appendix that occur after the introduction of immunobiological drugs. We conducted the histological studies of the vermiform appendix of rabbits after performing an antigenic stress using the vaccine against streptococcal and staphylococcal infections of animals along with the preventive agent «Pneumo-Pro» separately and combined with Selefer, a selenium-containing immunostimulant. Histological studies of the rabbits’ vermiform appendix performed after the parenteral introduction of immunoprophylactic drugs revealed significant structural changes in the lymphoid apparatus: there is a significant amount of lymphoblasts in the center of submucosal lymphoid nodes; mitosis of lymphocytes is often visualized; large, medium and small lymphocytes as well as macrophages locate in the dome of submucosal lymphoid nodes; there are numerous volumetric clusters of lymphoid tissue that form submucosal clusters of lymphoid nodes in the plate and submucosal basis of the appendix; the peripheral part of the lymphoid nodes and the interfollicular area contain a significant number of T-lymphocytes; the vast majority of secondary lymphoid follicles are cone-shaped; appendix crypts contain a large number of exocrinocysts.

The Appendix as a Viable Source of Neural Progenitor Cells to Functionally Innervate Bioengineered Gastrointestinal Smooth Muscle Tissues

Appendix-derived neural progenitor cells (NPCs) have both neurogenic and gliogenic potential, but use of these cells for enteric neural cell therapy has not been addressed. The objective of this study was to determine whether NPCs obtained from the appendix would differentiate into enteric neural subsets capable of inducing neurotransmitter-mediated smooth muscle cell (SMC) contraction and relaxation. NPCs were isolated from the appendix and small intestine (SI) of rabbits. Bioengineered internal anal sphincter constructs were developed using the same source of smooth muscle and innervated with NPCs derived from either the appendix or SI. Innervated constructs were assessed for neuronal differentiation markers through Western blots and immunohistochemistry, and functionality was assessed through force-generation studies. Expression of neural and glial differentiation markers was observed in constructs containing appendix- and SI-derived NPCs. The addition of acetylcholine to both appendix and SI constructs caused a robust contraction that was decreased by pretreatment with the neural inhibitor tetrodotoxin (TTX). Electrical field stimulation caused relaxation of constructs that was completely abolished in the presence of TTX and significantly reduced on pretreatment with nitric oxide synthase inhibitor (Nω-nitro-l-arginine methyl ester hydrochloride [l-NAME]). These data indicate that in the presence of identical soluble factors arising from intestinal SMCs, enteric NPCs derived from the appendix and SI differentiate in a similar manner and are capable of responding to physiological stimuli. This coculture paradigm could be used to explore the nature of the soluble factors derived from SMCs and NPCs in generating specific functional innervations. This study demonstrates the ability of neural stem cells isolated from the appendix to differentiate into mature functional enteric neurons. The differentiation of neural stem cells from the appendix is similar to differentiation of neural stem cells derived from the gastrointestinal tract. The appendix is a vestigial organ that can be removed with minimal clinical consequence through laparoscopy. Results presented in this paper indicate that the appendix is a potential source of autologous neural stem cells required for cell therapy for the gastrointestinal tract.

Atypical localization of myenteric ganglia in the human appendical wall: a comparative study with animal appendix

AbstractThe presence of well developed appendices in some animals when compared to humans has led to speculation that appendix is a vestigial organ. Increasing number of studies have revealed that the appendix serves as an important organ in humans. The function of animal appendix, and the differences between species remain poorly understood. In this study we examined human myenteric plexus and compared them with animal studies. Appendices were obtained from five young adults in which the appendix was found to be normal after removal. Fixed appendix cryosections were examined by immunofluorescence methods using neuronal marker antibodies to neurofilaments and beta III tubulin. Both antibodies stained myenteric ganglia which were arranged in an apparently irregular pattern in human appendix wall. We observed unexpected localization of myenteric ganglia in the subserosa often accompanied by rarely occurring ganglia in the longitudinal muscle layer. These ganglia were of different sizes and shapes and unequally distributed under a thin layer of serosa. Our findings raise many questions about the possible role of irregular and atypical myenteric ganglia localization in relation to altered motility and subsequent pathogenesis of the appendix in inflammatory disease in humans. On the other hand, studies of the literature have revealed simplicity in the organization of myenteric plexus, e.g., in well-developed rabbit appendix. In addition, appendicitis in animals is restricted to in apes with similarly shaped appendix to humans.

Diversification of the primary antibody repertoire begins during early follicle development in the rabbit appendix

Rabbits generate a diversified primary antibody repertoire by somatically mutating, in gut-associated lymphoid tissue (GALT), an initial repertoire that is limited by preferential rearrangement of the 3′-most IGVH gene segment. To determine when repertoire diversification begins in GALT, we performed in situ hybridization on neonatal rabbit appendix sections with an activation-induced cytidine deaminase (AID) riboprobe, because AID is required for the mutational processes that diversify the primary antibody repertoire. We first detected AID mRNA expression around 1 week of age, in the basal region of developing follicles. By PCR-amplifying V–D–J genes from AID mRNA+ B cells isolated by laser capture microdissection, we found evidence of somatic hypermutation, and one likely instance of somatic gene conversion. Our results suggest that V–(D)–J gene diversification begins during early postnatal appendix development, in B cells stimulated to enter a proliferative program by signals derived from select intestinal commensals.

Trace elements changes in the appendix of rabbit infected with Eimeria coecicola

The parasitic protozoa, Eimeria coecicola, causes intestinal coccidiosis in rabbits and, thereby, enormous economic losses in rabbit farms. This study aimed to investigate the trace elements changes in the appendix of infected rabbits with E. coecicola. Rabbits were orally infected with 50000 sporulated oocysts of E. coecicola, began to shed parasitic oocysts with their faeces on day 5 post-insemination (p.i.) and approximately 1.1 million oocysts were maximally shedded on day 7 p.i. At maximal shedding, animals were euthanized and appendiceal samples were collected. The coccidial infection was accompanied with a decrease in weight of infected rabbits reaching 25% at day 7 p.i. Our results showed that the concentration of iron, boron, cadmium, cobalt, manganese and zinc was significantly increased due to E. coecicola infection. On the contrary, the concentration of sodium, potassium and calcium was not significantly changed. Also the number of goblet cells in the appendiceal villi was significantly decreased. It was shown that E. coecicola infection has induced an alteration in the level of some trace elements as well as goblet cells. Key words: Trace elements, Eimeria coecicola, rabbits.

Gene expression in rabbit appendices infected with Eimeria coecicola

Eimeria coecicola causes intestinal coccidiosis in rabbits and, thereby, enormous economic losses in rabbit farms. Here, we investigate the final target site of E. coecicola, the appendix of rabbits, at the level of gene expression. Rabbits, orally infected with E. coecicola, begin to shed parasitic oocysts with their feces on day 5 p.i., and approximately 1.1 million oocysts are maximally shedded on day 7 p.i. At maximal shedding, the appendix has increased in size by about 2–3-folds and reveals increased hemorrhage which is associated with increases in nitrite/nitrate, malondialdehyde and catalase activity and a decrease in glutathione. Agilent 2-color oligo whole rabbit genome microarray, in combination with quantitative real-time PCR, detects 45 and 36 genes whose expression is more than 2-fold up- and down-regulated, respectively, by E. coecicola infection on day 7 p.i. The most dramatic increase by approximately 50-fold reveals the mRNA of the pro- and anti-inflammatory pleiotropic cytokine interleukin 6 (IL-6), whereas the largest decrease by approximately 13-fold is detected for mRNAs encoding for DBP, SULT3A1, CRP and glutathione-S transferase. Also, there are up- and down-regulations in the expression of genes encoding diverse regions of antibodies. Our data suggest that IL-6 plays a central role in the infection of the appendix of rabbits by E. coecicola, presumably involved in both pathological injuries, host defences and healing processes.

Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development

Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4–7.4 in the guinea pigs and rabbits, whereas lower pH (6.1–6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0–6.4) and colon (6.1–6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51 g, 153 g and 1546 g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig > rabbit > pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pig < rabbit < pig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies.

Onset of Antibody Repertoire Diversification in the Rabbit Appendix (81.17)

Abstract Unlike mice and humans, rabbits generate their primary antibody repertoire by somatically diversifying V(D)J genes in gut-associated lymphoid tissues (GALT). Rabbit V(D)J genes are diversified by somatic hyper-point mutation and somatic gene conversion, both of which require activation-induced cytidine deaminase (AID). To determine when repertoire diversification begins, we examined AID expression in neonatal rabbit appendix by in situ hybridization. We first detected AID mRNA expression at one week of age, in B cells in the basolateral region of appendix follicles. We asked whether AID+ B cells were undergoing V(D)J gene diversification by using laser capture microdissection (LCM) to isolate AID+ and AID- B cells from 1-week-old appendix follicles. We RT-PCR-amplified and cloned VDJ genes from the two B cell populations, and searched for evidence of somatic diversification by comparing their nucleotide sequences to those of the appropriate germline genes. We found somatic gene conversion events in the VDJ genes from AID+ B cells, but not in those from AID- B cells. These results demonstrate that diversification of the rabbit primary antibody repertoire begins around 1 week of age, in B cells residing at the basolateral region of appendix follicles. This work was supported by NIH Grant 1 RO1 AI49458-01A1.

Ovine herpesvirus 2 structural proteins in epithelial cells and M-cells of the appendix in rabbits with malignant catarrhal fever

Sheep-associated malignant catarrhal fever (MCF), caused by Ovine herpesvirus 2 (OvHV-2), is a usually fatal disease of various ruminants and swine. A system for propagation of OvHV-2 in vitro has not yet been identified, although persistently infected cells have been derived from diseased animals and used to establish an animal model in rabbits. OvHV-2 structural proteins have not been detected in diseased animals and the pathogenesis of OvHV-2 infection is poorly understood. Recently, the genomic sequence of OvHV-2 has been determined, which allowed to predict the amino acid sequences of putative OvHV-2 structural proteins. Based on those predictions, we have generated antisera against two putative structural proteins (ORF43 and ORF63) of OvHV-2 in order to detect sites of active virus replication in experimentally OvHV-2-infected rabbits with signs of MCF. Although histological lesions typical of MCF were detected in multiple tissues, those sera detected viral capsid and tegument antigens exclusively in the appendix but not in other tissues of rabbits with MCF. More specifically, those viral proteins were detected in epithelial cells as well as in M-cells. However, in situ hybridization revealed that ORF63 mRNA was present in epithelial cells of infected rabbits but not in M-cells. Our data suggest that active OvHV-2 replication takes place in certain tissues of animals with MCF and that M-cells may play a role in the pathogenesis of MCF.

Expression and localization of rabbit B-cell activating factor (BAFF) and its specific receptor BR3 in cells and tissues of the rabbit immune system

Rabbits are widely used for vaccine development, and investigations of human infectious and autoimmune diseases such as Systemic Lupus Erythematosus (SLE). For these applications, we cloned, sequenced and expressed rabbit B-cell Activating Factor (BAFF), and localized BAFF in cells and tissues of the rabbit immune system. The rabbit homolog of the human BAFF binding site (miniBR3 peptide) within the BAFF-specific receptor BR3 was synthesized. This 26-residue core domain binds to recombinant rabbit BAFF protein. Flow cytometric analyses using purified recombinant rabbit BAFF combined with real-time PCR findings revealed that BAFF detected on peripheral blood B-cells from normal rabbits is probably complexed to BAFF receptors rather than produced by the B-cells. BAFF was detected in developing appendix of young rabbits by immunohistochemical staining suggesting that BAFF plays a role during the period following birth when rabbit B-cell development and pre-immune antibody repertoire diversification and selection is occurring.

Microbial Induction of T Cell Areas in the Rabbit Appendix

The rabbit appendix contains multiple B cell follicles separated at their sub‐apical regions by well‐defined T cell areas. We found, by RNA in situ hybridization, that the T cell chemoattractant SLC (secondary lymphoid tissue chemokine, or CCL21) is highly expressed in the T cell areas of adult rabbit appendix. We unexpectedly also found, however, that the localized expression of SLC differs dramatically in early neonatal appendix. SLC was first expressed about two days after birth in a continuous layer beneath the B cell clusters. As B cells accumulated and began proliferating over subsequent days, developing follicles grew down through the layer of SLC expression, ultimately generating the characteristic organization of B and T cell areas seen in adult appendix. Furthermore, by introducing bacterial isolates into appendices rendered germfree through ligation at birth, we found that T cell area development is dependent on intestinal commensals, and that individual commensals differed in their ability to induce T cell areas. Microbial induction of T cell areas in the rabbit appendix might be important for supporting B cell proliferation and V(D)J gene diversification in appendix follicles, which generate the primary antibody repertoire. This work was supported by NIH grant 1 RO1 AI49458‐01A1.

Microbial induction of B and T cell areas in rabbit appendix

Gut-associated lymphoid tissue (GALT) development requires interaction with the intestinal microbiota. Because murine secondary lymphoid tissue development is driven by positive feedback interactions between B cells and stromal cells, we used in situ hybridization to determine whether intestinal commensals influence such interactions during rabbit appendix development. The features of positive feedback interactions we examined (CXCL13 mRNA expression, B cell accumulation and FDC differentiation) increased during early follicle development, but stalled in the absence of intestinal commensals. These features were reinitiated by commensals that stimulated follicle development and intrafollicular B cell proliferation. Our results suggest that rabbit appendix follicles develop in two phases: an initial phase of B cell recruitment to nascent follicles, possibly through positive feedback interactions, and a subsequent phase of intrafollicular B cell proliferation stimulated by intestinal commensals. In addition, we found that intestinal commensals stimulate appendix CCL21 mRNA expression and T cell area formation.

Temporal development of B and T cell areas in the neonatal rabbit appendix. (90.14)

Abstract The rabbit appendix is organized structurally into multiple B cell follicles separated, at their sub-apical regions, by well-defined T cell areas. We found, by RNA in situ hybridization, that the B cell chemoattractant CXCL13 (B-lymphocyte chemoattractant, or BLC) is highly expressed in the B cell follicles. In addition, we found that the T cell chemoattractant CCL21 (secondary lymphoid tissue chemokine, or SLC) is highly expressed in the T cell areas. The localized expression of these chemoattractants likely organizes the B and T cell areas of the appendix. Surprisingly, however, we found that the localized expression of CXCL13 and CCL21 differs dramatically in early neonatal appendix. At two days after birth, CXCL13 expression was confined to the appendix domes and CCL21 expression was localized in a continuous layer significantly beneath the domes. Over subsequent days, as B cells accumulated in the domes and began proliferating, developing follicles gradually distended downward through the layer of CCL21 expression, ultimately generating the characteristic organization of B and T cell areas seen in the adult appendix. This developmental process might be important in establishing an environment supportive of B cell proliferation and antibody repertoire diversification, which occur in the rabbit appendix between 3 and 6 weeks of age.

De novo expression of MECA‐79 glycoprotein‐determinant on developing B lymphocytes in gut‐associated lymphoid tissues

Rabbit is one of several species that depend on development of B lymphocytes in gut-associated lymphoid tissues for primary immunoglobulin-repertoire diversification. The rabbit appendix is an important site of early B-lymphocyte development. We previously reported that peripheral lymph node addressin detected by monoclonal antibody (mAb) MECA-79 played a role in recruitment of immature blood-borne B cells into neonatal rabbit appendix. Here, we report expression of an approximately 127 000 MW O-linked sulphated proteoglycan on developing B cells in appendix and Peyer's patches recognized by the mAb MECA-79. Binding of the mAb to B lymphocytes was sensitive to enzyme treatment with O-sialoglycoprotease and expression was partially inhibited by sodium chlorate, a metabolic inhibitor of sulphation. The proportions of MECA-79(+) B lymphocytes gradually increased from < 0.5% at 3 days to > 70% at 6 weeks in appendix and Peyer's patches. The proportions of MECA-79(+) B lymphocytes in spleen and peripheral blood were very low (0.5-2%). However, the MECA-79 determinant was detected on B cells in splenic germinal centres after immunization. In situ labelling of appendix cells showed that the MECA-79 determinant was expressed on fluorescein-labelled B lymphocytes that migrated from appendix into mesenteric lymph nodes. B-cell MECA-79 may be involved in interactions with T cells and/or dendritic cells. Alternatively, because we found that lymphatic endothelium in the thymus-dependent area of appendix, a site for lymphocyte exit, expressed P-selectin (CD62P), interaction of the MECA-79 determinant on B cells with CD62P may have a role in the exit of B lymphocytes from rabbit appendix.

Experimental lesions of the rabbit's appendix

Experimental lesions of the rabbit's appendix

CD5 + B cells are preferentially expanded in rabbit appendix: The role of CD5 in B cell development and selection

Although only a small proportion of mouse and human B cells are CD5 +, most adult rabbit B cells express CD5. However, CD5 was not detectable on the majority of B cells in neonatal appendix 1 and 3 days after birth. Cell trafficking studies demonstrated that CD5 + and CD5 − CD62L + B cells from bone marrow migrated into appendix. There, CD5 + B cells were preferentially expanded and predominated by ∼2 weeks of age. In mutant ali/ ali rabbits, VHa2 + B cells develop through gene conversion-like alteration of rearranged VH genes upstream of deleted VH1a2. Correlated appearance of individual CD5 + germinal centers and VHa2 + B-cells in mutant appendix suggests that CD5 binding positively selects cells with a2 + framework regions that bind CD5. Following negative and positive selection, cells with diversified rearranged heavy- and light-chain sequences exit appendix, migrate to peripheral tissues and constitute the preimmune repertoire of CD5 + B cells that encounter foreign antigens.

Bacterial-induced Inflammation in Germ-free Rabbit Appendix

The intestinal ecosystem is defined by a series of interactions between the microbiota, the mucosal epithelium, and the gut-associated lymphoid tissue (GALT). Perturbations in the fine balance of the interactions between these components can result in gastrointestinal diseases such as inflammatory bowel disease (IBD). The pathophysiology of IBD is thought to develop as a result of dysregulated mucosal immune responses to normal luminal microflora. Several animal models for IBD have been developed and underscore the role of the immune system in development of disease. Most of the existing animal models studying IBD are based on the use of chemically induced IBD or of genetically modified and germ-free animals. It is, however, important to study inflammatory responses that can develop from interactions between bacteria, the mucosal epithelium, and GALT in animals that are not genetically modified or immunocompromised. In this report, we document the use of a germ-free ligated rabbit appendix model to induce inflammatory changes in response to specific bacteria. With the introduction of a Bacteroides vulgatus isolate from humans into the germ-free ligated appendix, we found chronic inflammatory changes, including glandular distortion, gland drop-out, decreased goblet cells, and crypt abscess formation. However, with the introduction of other experimental luminal contents, we observed no inflammation. These results show that specific microbial composition can induce inflammation. We suggest that this model may be useful to study the mechanism by which specific bacteria establish inflammatory responses in the gut.

Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix

Young rabbit appendix is a homologue of chicken bursa of Fabricius; both are crucial sites for preimmune B-cell repertoire diversification. Here, we report that appendix regulates precursor lymphocyte recruitment for further development by modulating the sites of extravasation. The total area of peripheral node addressin-positive (PNAd +) high endothelial venules (HEVs) increased from 1 day to 1 week after birth, remained constant up to 2 weeks and declined to a low and persistent amount by 3 weeks. In normal 1-week and manipulated 5-week appendix where growth of follicles was retarded, PNAd + HEVs were present in the basolateral sides of B-cell follicles whereas, in normal 5-wk-appendix these were restricted to T-cell areas. The PNAd was expressed on the lumenal surface of HEVs. The proportions of CD62L + B cells in appendix declined from ∼40% at 3 days to 2–3% at 4 weeks. In lymphocyte transfer experiments, CD62L + B cells were preferentially recruited compared with CD62L − B cells, anti-PNAd antibody blocked migration of B cells by ∼50%, and 100 times more B cells were recruited in 1-week compared to 6-week appendix. Thus, a unique spatiotemporal expression pattern of PNAd + HEVs is associated with development of B-cell follicles. This regulates migration of blood-borne B-lymphocytes into developing appendix by interacting with CD62L.