<P> Once a BCR binds a TD antigen, the antigen is taken up into the B cell through receptor - mediated endocytosis, degraded, and presented to T cells as peptide pieces in complex with MHC - II molecules on the cell membrane . T helper (T) cells, typically follicular T helper (T) cells, that were activated with the same antigen recognize and bind these MHC - II - peptide complexes through their T cell receptor (TCR). Following TCR - MHC - II - peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL - 4 and IL - 21 . CD40L serves as a necessary co-stimulatory factor for B cell activation by binding the B cell surface receptor CD40, which promotes B cell proliferation, immunoglobulin class switching, and somatic hypermutation as well as sustains T cell growth and differentiation . T cell - derived cytokines bound by B cell cytokine receptors also promote B cell proliferation, immunoglobulin class switching, and somatic hypermutation as well as guide differentiation . After B cells receive these signals, they are considered activated . </P> <P> Now activated, B cells participate in a two - step differentiation process that yields both short - lived plasmablasts for immediate protection and long - lived plasma cells and memory B cells for persistent protection . The first step, known as the extrafollicular response, occurs outside lymphoid follicles but still in the SLO . During this step activated B cells proliferate, may undergo immunoglobulin class switching, and differentiate into plasmablasts that produce early, weak antibodies mostly of class IgM . The second step consists of activated B cells entering a lymphoid follicle and forming a germinal center (GC), which is a specialized microenvironment where B cells undergo extensive proliferation, immunoglobulin class switching, and affinity maturation directed by somatic hypermutation . These processes are facilitated by T cells within the GC and generate both high - affinity memory B cells and long - lived plasma cells . Resultant plasma cells secrete large amounts of antibody and either stay within the SLO or, more preferentially, migrate to bone marrow . </P> <P> Antigens that activate B cells without T cell help are known as T cell - independent (TI) antigens and include foreign polysaccharides and unmethylated CpG DNA . They are named as such because they are able to induce a humoral response in organisms that lack T cells . B cell response to these antigens is rapid, though antibodies generated tend to have lower affinity and are less functionally versatile than those generated from T cell - dependent activation . </P> <P> As with TD antigens, B cells activated by TI antigens need additional signals to complete activation, but instead of receiving them from T cells, they are provided either by recognition and binding of a common microbial constituent to toll - like receptors (TLRs) or by extensive crosslinking of BCRs to repeated epitopes on a bacterial cell . B cells activated by TI antigens go on to proliferate outside lymphoid follicles but still in SLOs (GCs do not form), possibly undergo immunoglobulin class switching, and differentiate into short - lived plasmablasts that produce early, weak antibodies mostly of class IgM, but also some populations of long - lived plasma cells . </P>

Where do b cells and t cells mature