Naive B-cells

Tsuji, T., et al. Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin, J. Immunol., 152, 4417, 1994. 

Beissert S, Gueler F, Loser K, Gunzer M Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse. Blood 2007 110 1519-1529. 

A limitation is that the effector cells only have a short half-life (2-A days) so that a subsequent invasion by the same pathogen would require the establishment of another cellular cascade by a few remaining naive B-cells, i.e. it would be a slow response. To overcome this, during the first invasion, the cascade also results in the production of B-cells that have a memory of the antigens of the invading pathogen (Figure 17.10). Consequently, the cascade presented above can now be extended to take into account the memory cell ... 

Lymphoid dendritic cells promote negative selection in the thymus. This may be attributed to their ability to induce fas-mediated apoptosis. Based on their ability to cause apoptosis and their ability to eliminate self-reactive T cells, lymphoid dendritic cells exhibit a regulatory function instead of a stimulatory immune effector function. Myeloid dendritic cells also have differential effects. For example, T cells can be primed to selectively activate THi responses by CD14-derived myeloid dendritic cells. Naive B cells can be activated in the presence of CD40L and IL-2 to secrete IgM by CD34+, CD14-derived myeloid dendritic cells. This effect on naive B cells is not observed with CD la-derived dendritic cells. 

The final stage of B cell differentiation where the BCR repertoire is shaped is the germinal centre (GC) reaction. In the T cell dependent GC reaction, the BCR is adapted for its cognate antigen by somatic hypermutation (SMH) and class switch recombination (CSR), both of which are driven by activation induced cytidine deaminase (AID). Since AID induces targeted point mutations in the CDRs of the Ig HCs and Ig LCs, this can dramatically alter the BCR affinity or even its specificity. As AID activity may also result in the formation of an autoreactive BCR, a stringent counterselection of such self-reactive B cells is required. By analysis in human of the BCR repertoire of post-GC IgG+ memory B cells, it was demonstrated that indeed new auto-reactive B cells develop by SHM whereas 20% of naive B cells is self-reactive, up to 40% of the IgG+ memory B cells expressed a true de novo created self-reactive BCR. Apparently, lack of T cell help prevents activation of these self-... 

In humans, there are five isotypes of antibodies, IgG, IgA, IgD, IgE, and IgM, which are defined by the structures of their heavy chains and their abilities to form multimers (Figure 10.1) [8], IgG is the most abundant isotype present in serum with average serum concentrations ranging from 0.5 to 9mg/ml depending on the IgG subtype. This is followed by IgA (3mg/ml), IgM (1.5mg/ml), IgE (0.05 mg/ml), and IgD (trace). Each antibody isotype has unique functions. Critical functions of IgG include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), passive immunity, and regulation of B cells. Both IgM and IgD act as antigen receptors on naive B cells, and soluble, multimeric forms of IgM are involved in complement activation. IgA is involved in mucosal and passive neonatal immunity, while IgE is involved in immediate hypersensitivity [8],... 

Two types of switching can be defined first the switch from expression of IgM in early B cells to expression of IgM and IgD in naive B cells. This switch does not involve switch recombination but differential splicing of a long transcript the regulation of this process is unclear. This switch happens at a defined stage of B cell ontogeny and presumably provides the naive B cell with a receptor (IgD) required for the activation by antigen. 

Upon activation, the naive B cell stops to express IgD, starts secretion of IgM and, at a high frequency, is induced to a second type of switching (Fig. 3). This switch from IgM to any other immunoglobulin class is performed by repeated recombinations within and between switch regions through several rounds of replication. It occurs only in induced cells and on both IgH alleles. Lymphokines -switch factors - may be required to determine which switch regions are open for... 

Du MQ, Liu H, Diss TC, et al. Kaposi sarcoma-associated herpesvirus infects monot)fpic (IgM lambda) hut polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders. Blood 2001 97 2130-2136. 

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