Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens.

Abstract

To examine the in vivo function of IgD we generated mice deficient for IgD by gene targeting. The IgDmice show a reduced B-cell compartment with 30-50% less B cells in the spleen and lymph nodes but show a normal pre-B-cell compartment. The surface-IgD-B cells express two to three times more surface IgM than B cells ofcontrol animals. Serum concentrations of the immunoglobuln isotpes of IgDmice are almost normal, indicating that surface-IgD expression is not necessary for class switching of B cells. Immunization experiments showed that IgD-mice could respond well to thymus-dependent and -independent antigens. After immunization normal germinal centers developed in the IgD-mice. cells (7, 8). In vivo the functions attributed to the engagement of sIgD vary from the acquisition of resistance to tolerance induction (10-12) and the initiation ofthe B-cell response (13) to a role in B-cell memory (6,14,15). Some ofthese functions were studied by using chronic anti-IgD treatment from birth (16,17), by in vitro sorting of sIgD+ and sIgD-B cells (10,18,19), by enzymatic removal of sIgD in vitro (11), or by transgenic mouse models (20). Discrepancies of results were found in these studies that could be generated by the nature of the indirect experimental systems used. Roes and Rajewsky (21) PCR and Southern Blots. ES cell clones were picked and prepared for a nested primer PCR analysis, as described (35). Genomic DNA for Southern blotting was prepared from ES cells or from the tail ends of mice.Flow Cytometric Analysis (FCM). FCM of single-cell suspensions of lymphatic organs was done on a FACScan flow cytometer (Becton Dickinson). The antibodies used for staining were either (i) biotinylated and counterstained with streptavidin-phycoerythrin 11-26C (anti-IgD, from J. Kearney, University of Alabama, Birmingham) ( Fig. 2 a and b), M41 (anti-IgM) (27) (Fig. 2 c and d), B7/6 (anti-IgM) (27) (Fig. 2 g and h) or (ii) conjugated with fluorescein isothiocyanate M41 (anti-IgM) (Fig. 2 a and

Natural Autoreactive B Cells in Transgenic Mice Reproduce an Apparent Paradox to the Clonal Tolerance Theory

“…Tg mice expressing mb IgD and IgM have an increased mature B cell pool (29) compared with tg mice expressing only mb IgM. Our results, even though originating from single IgM and IgM/IgD tg lines, are consistent with these data and those of others (30). nAAb B cells exit from the bone marrow whether they express IgD or not, but the proportion of peripheral immature B cells (AA 4.1 positive, CD23 negative) is significantly higher in tg mice that express only IgM.…”

A novel chimeric Ig heavy chain from a teleost fish shares similarities to IgD

“…In contrast, IgD is a class of antibody that is considered to have evolved relatively recently, having been described only in primates and rodents (7)(8)(9)(10). Although the function, biochemistry and genetics of IgD have been the subject of intense interest (11)(12)(13)(14)(15)(16)(17) gene targeting (knockout) experiments revealed that IgD had a relatively minor functional role in immune responses in the mouse (18,19). We report here the results of studies that identify a complex homolog of the IgD heavy (H) (␦) chain in the channel catfish (Ictalurus punctatus).…”

IgD+IgM– B cells mount immune responses that exhibit altered antibody repertoire

“…IgD-deficient mice respond well to T cell-independent and -dependent antigens, but affinity maturation is delayed in the early primary response compared to control animals [6], suggesting that there may be differences in the function of IgM and IgD as antigen receptors. In addition, it has been shown that IgD -/-mice have 30-50% fewer B cells in the spleen and lymph nodes than IgD +/+ mice [7], suggesting that IgD may have a role in B cell homeostasis. In IgM -/-mice, B cell development and maturation proceed normally, with IgD replacing IgM [8].…”